AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the reg...AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the regulatory effects of fluoxetine(FLX)treatment and binocular form deprivation(BFD)on these indices.METHODS:Wistar rats were assigned to three experimental cohorts:1)Age-related groups:postnatal week(PW)1,PW3,PW5,PW7,and PW9;2)FLX treatment duration groups:FLX 0W,FLX 2W,FLX 4W,FLX 6W,and FLX 8W;3)Intervention groups:control(Cont),FLX,BFD,and BFD+FLX.The levels of PNNs,PV,and PNNs/PV coexpression in the visual cortex were detected and analyzed.RESULTS:The density of PV-positive cells and the coexpression of PNNs and PV increased gradually with the maturation of the visual cortex(b=0.960,P<0.01).The ratio of PV-positive cells surrounded by PNNs to total PV-positive cells(PNNs+/PV+/total PV+)was significantly decreased in the FLX 4W group(χ^(2)=9.03,P=0.003).There was no significant difference in the PNNs+/PV+/total PV+ratio between the FLX and BFD groups(χ^(2)=1.08,P=0.161),but a significant difference was observed between the BFD+FLX group and the BFD group(χ^(2)=5.82,P<0.01).CONCLUSION:The number of PV-positive neurons and PNNs-surrounded PV neurons in the rat visual cortex increases postnatally and reaches adult levels by postnatal week 7.Chronic FLX treatment downregulates these expressions.Combined 4-week FLX treatment and BFD exerts a more significant inhibitory effect on the PNNs+/PV+/total PV+ratio than either intervention alone.展开更多
BACKGROUND Depression is a common,chronic,and recurrent mood disorder that has become a worldwide health hazard.Fluoxetine hydrochloride,a common treatment method,can inhibit 5-hydroxytryptamine(5-HT)recycling in the ...BACKGROUND Depression is a common,chronic,and recurrent mood disorder that has become a worldwide health hazard.Fluoxetine hydrochloride,a common treatment method,can inhibit 5-hydroxytryptamine(5-HT)recycling in the presynaptic membrane;however,the efficacy of a single drug is inadequate.At present,mildto-moderate depression can be treated with acupuncture of ghost caves,but the clinical curative effect of combined therapy with fluoxetine hydrochloride has not been sufficiently reported.AIM To evaluate the clinical effect of acupuncture at ghost points combined with fluoxetine hydrochloride in the treatment of mild-to-moderate depression.METHODS This retrospective study included 160 patients with mild-to-moderate depression who were admitted to Shanghai Hospital of Integrated Traditional Chinese and Western Medicine,Affiliated to Shanghai University of Traditional Chinese Medicine,between January 2022 and June 2023.Patients were separated into a single-agent group(fluoxetine hydrochloride treatment,n=80)and a coalition group(fluoxetine hydrochloride treatment combined with acupuncture at ghost points,n=80).Pre-treatment symptoms were recorded,and the clinical curative effect and adverse reactions[Asberg Antidepressant Side Effects Scale(SERS)]were assessed.Depression before and after treatment[Hamilton Depression Scale(HAMD)-24],neurotransmitter levels[5-HT,norepinephrine(NE),dopamine(DA)],oxidative stress indicators[superoxide dismutase(SOD),malondialdehyde(MDA)],and sleep quality[Pittsburgh Sleep Quality Index(PSQI)]were compared.RESULTS The total efficacy rate was 97.50%in the coalition group and 86.25%in the single-agent group(P<0.05).After 2,4,6,and 8 wk of treatment,the HAMD,self-rating depression scale,and SERS scores of the coalition and single-agent groups decreased compared with pre-treatment,and the decrease was more significant in the coalition group(P<0.05).After 8 wk of treatment,the levels of NE,DA,5-HT,and SOD in the coalition and single-agent groups increased,while the levels of MDA decreased;the increases and decrease in the coalition group were more significant(P<0.05).The PSQI scores of the coalition and single-agent groups decreased,and the decrease was more significant in the coalition group(P<0.05).CONCLUSION Acupuncture at ghost points combined with paroxetine tablets can safely improve depressive symptoms and sleep disorders,regulate neurotransmitter levels,and reduce stress responses in patients with mild-to-moderate depression.展开更多
Posttraumatic stress disorder(PTSD)is a complex mental disorder notable for traumatic experience memory.Although current first-line treatments are linked with clinically important symptom reduction,a large proportion ...Posttraumatic stress disorder(PTSD)is a complex mental disorder notable for traumatic experience memory.Although current first-line treatments are linked with clinically important symptom reduction,a large proportion of patients retained to experience considerable residual symptoms,indicating pathogenic mechanism should be illustrated further.Recent studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory preservation.However,its role in PTSD remains to be elucidated.In this study,we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and hippocampus.Fluoxetine,but not risperidone or sertraline,has a more profound rescue effect on neuropsychological behaviors and myelin abnormalities.Further mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt signaling.Our data demonstrated the correlation between PTSD and abnormal myelination,suggesting that the oligodendroglial lineage could be a target for PTSD treatment.展开更多
The frequent detection of pharmaceutical compounds in the environment has led to a growing awareness,which may pose a major threat to the aquatic environment.In this study,photodegradation(direct and indirect photolys...The frequent detection of pharmaceutical compounds in the environment has led to a growing awareness,which may pose a major threat to the aquatic environment.In this study,photodegradation(direct and indirect photolysis)of two different dissociation states of fluoxetine(FLU)was investigated in water,mainly including the determination of photolytic transition states and products,and the mechanisms of indirect photodegradation with·OH,CO_(3)^(*-)and NO_(3)^(*).The main direct photolysis pathways are defluorination and C–C bond cleavage.In addition,the indirect photodegradation of FLU in water is mainly through the reactions with·OH and NO_(3)^(*),and the photodegradation reaction with CO_(3)^(*-)is relatively difficult to occur in the water environment.Our results provide a theoretical basis for understanding the phototransformation process of FLU in the water environment and assessing its potential risk.展开更多
Although depression may affect patients＇ recovery and even their survival rate after stroke,it is often overlooked or inadequately managed.And data regarding the treatment efficacy and safety of fluoxetine in this se...Although depression may affect patients＇ recovery and even their survival rate after stroke,it is often overlooked or inadequately managed.And data regarding the treatment efficacy and safety of fluoxetine in this setting are inconsistent.We aimed to systematically assess those two indices in patients with post-stroke depression （PSD）.Through a systematic literature search in 10 biomedical databases,244 articles were first identified,through which we collected and evaluated a total of 600 patients identified from 11 RCTs.The meta-analysis with Revman software indicated that fluoxetine was more effective than placebo,the combined results of 9 RCTs showed that fluoxetine decreased the depression rating scale scores significantly compared with placebo,and the pooled weighted mean difference （WMD） was 0.44 （95% CI-0.03 to 0.92）.Moreover,time-dependent effects were also observed.No consistent evidence was found for its positive effects on the recovery of neurological impairments and improvements in activities of daily living （ADL）.Six studies reported rate of adverse effects in both fluoxetine groups and control groups and showed no significant difference between them （OR=0.03,95% CI-0.00 to 0.07）.This meta-analysis suggested that fluoxetine may be effective and safe for patients with PSD and it may have time-dependent effects.展开更多
Depression is a debilitating psychiatric disorder with a huge socioeconomic burden, and its treatment relies on antidepressants including selective serotonin reuptake inhibitors(SSRIs). Recently, the melatonergic syst...Depression is a debilitating psychiatric disorder with a huge socioeconomic burden, and its treatment relies on antidepressants including selective serotonin reuptake inhibitors(SSRIs). Recently, the melatonergic system that is closely associated with the serotonergic system has been implicated in the pathophysiology and treatment of depression. However, it remains unknown whether combined treatment with SSRI and melatonin has synergistic antidepressant effects. In this study, we applied a sub-chronic restraint stress paradigm, and evaluated the potential antidepressant effects of combined fluoxetine and melatonin in adult male mice. Sub-chronic restraint stress(6 h/day for 10 days) induced depression-like behavior as shown by deteriorated fur state, increased latency to groom in the splash test, and increased immobility time in the forced-swim test. Repeated administration of either fluoxetine or melatonin at 10 mg/kg during stress exposure failed to prevent depression-like phenotypes. However,combined treatment with fluoxetine and melatonin at theselected dose attenuated stress-induced behavioral abnormalities. Moreover, we found that the antidepressant effects of combined treatment were associated with the normalization of brain-derived neurotrophic factor(BDNF)–tropomyosin receptor kinase B(Trk B) signaling in the hippocampus, but not in the prefrontal cortex. Our findings suggest that combined fluoxetine and melatonin treatment exerts synergistic antidepressant effects possibly by restoring hippocampal BDNF–Trk B signaling.展开更多
OBJECTIVE: To investigate the effects of WAA combined with fluoxetine in the clinical treatment of post-stroke depression(PSD).METHODS: In this randomized, controlled and single-blind trial, 105 PSD patients who met t...OBJECTIVE: To investigate the effects of WAA combined with fluoxetine in the clinical treatment of post-stroke depression(PSD).METHODS: In this randomized, controlled and single-blind trial, 105 PSD patients who met the inclusion criteria were randomly divided into three equal groups: Thin wrist-ankle acupuncture(WAA)group(Thin WAA needle + Fluoxetine), Thick WAA group(Thick WAA needle + Fluoxetine), and Sham WAA group(sham WAA needle + Fluoxetine). In this trial, the primary outcome was Hamilton Depression Scale(HAMD), while the secondary outcomes included Zung self-rating depression scale(SDS) and World Health Organization Quality of Life BREF(QQL).RESULTS: Ninety nine PSD patients completed all the treatment. The HAMD scores and SDS scores of all the three groups decreased after treatment(P <0.05);thick WAA group and thin WAA group decreased more obviously than the sham WAA group(P < 0.05). There was no significant difference between the QQL scores of the three groups(P >0.05). There was no significant difference in the scores of the three scales between the thick wrist ankle needles and the thin wrist ankle needles(P >0.05).CONCLUSION: The present study showed that WAA combined with fluoxetine can relieve the symptoms of depression after stroke. WAA therapy could improve the antidepressant effect of fluoxetine.展开更多
Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage(SAH) remain unclear. In this study, we aimed to evalua...Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage(SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury(EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine(10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier(BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1 b, IL-6, TNF-a, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.展开更多
BACKGROUND Depression affects more than 350 million people worldwide.In China,4.2%(54 million people)of the total population suffers from depression.Psychotherapy has been shown to change cognition,improve personality...BACKGROUND Depression affects more than 350 million people worldwide.In China,4.2%(54 million people)of the total population suffers from depression.Psychotherapy has been shown to change cognition,improve personality,and enhance the ability to cope with difficulties and setbacks.While pharmacotherapy can reduce symptoms,it is also associated with adverse reactions and relapse after drug withdrawal.Therefore,there has been an increasing emphasis placed on the use of non-pharmacological therapies for depression.The hypothesis of this study was that acupuncture at ghost points combined with fluoxetine would be more effective than fluoxetine alone for the treatment of depression.AIM To investigate the efficacy of acupuncture at ghost points combined with fluoxetine for the treatment of patients with depression.METHODS This randomized controlled trial included patients with mild to moderate depression(n=160).Patients received either acupuncture at ghost points combined with fluoxetine(n=80)or fluoxetine alone(control group,n=80).Needles were retained in place for 30 min,5 times a week;three treatment cycles were administered.The Mann–Whitney U test was used to compare functional magnet resonance imaging parameters,Hamilton depression rating scale(HAMD)scores,and self-rating depression scale(SDS)scores between the acupuncture group and control group.RESULTS There were no significant differences in HAMD or SDS scores between the acupuncture group and control group,before or after 4 wk of treatment.The acupuncture group exhibited significantly lower HAMD and SDS scores than the control group after 8 wk of treatment(P<0.05).The acupuncture group had significantly lower fractional Amplitude of Low Frequency Fluctuations values for the left anterior wedge leaf,left posterior cingulate gyrus,left middle occipital gyrus,and left inferior occipital gyrus after 8 wk.The acupuncture group also had significantly higher values for the right inferior frontal gyrus,right insula,and right hippocampus(P<0.05).After 8 wk of treatment,the effective rates of the acupuncture and control groups were 51.25%and 36.25%,respectively(P<0.05).CONCLUSION The study results suggest that acupuncture at ghost points combined with fluoxetine is more effective than fluoxetine alone for the treatment of patients with mild to moderate depression.展开更多
Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity.The overall prevalence of geriatric depression with clinically significant symptoms is curre...Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity.The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise.Recent studies have demonstrated that altered expressions of long non-coding RNAs(lncRNAs)in the brain affect neurodevelopment and manifest modulating functions during the depression.However,most lncRNAs have not yet been studied.Herein,we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors,as well as their corresponding response following antidepressant fluoxetine treatment.A chronic unpredictable mild stress(CUMS)mouse model was applied.A sixweek fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors.In addition,differential expression analysis of lncRNAs was performed following RNA-sequencing.A total of 282 lncRNAs(134 up-regulated and 148 down-regulated)were differentially expressed in CUMS-induced mice relative to non-stressed counterparts(P<0.05).Moreover,370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention.Gene Ontology(GO)analyses showed an association between significantly dysregulated lncRNAs and protein binding,oxygen binding,and transport activity,while the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways.Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus.The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.展开更多
Objective: This study is to investigate the clinical therapeutic effects and safety of treating mild or moderate depression with somatic symptoms with electroacupuncture combined with Fluoxetine. Methods: 95 cases of ...Objective: This study is to investigate the clinical therapeutic effects and safety of treating mild or moderate depression with somatic symptoms with electroacupuncture combined with Fluoxetine. Methods: 95 cases of mild or moderate depression with somatic symptoms were randomly divided into a Fluoxetine group, and an electroacupuncture plus Fluoxetine group. Hamilton Depression Scale (HAMD) was used for the assessment of clinical therapeutic effects and Treatment Emergent Symptom Scale (TESS) was used for assessment of adverse reactions. Results: The total effective rate was 77.27% in the Fluoxetine group and 78.26% in the electroacupuncture plus Fluoxetine group, showing no statistically significant difference between these two groups (P>0.05). However, the treatment took effect after two weeks in the electroacupuncture plus Fluoxetine group but after four weeks in Fluoxetine group. During this time, a better therapeutic effect on depression with mild or moderate somatic symptoms was found in the electroacupuncture plus Fluoxetine group, which also had fewer adverse reactions than the Fluoxetine group. Conclusion: Electroacupuncture combined with Fluoxetine takes effect faster for relieving the somatic symptoms with fewer adverse reactions. It is worth popularizing clinically.展开更多
Anxiety is a very common mental disorder among neurological diseases. Some herbs have soothing effects and play an important role in reducing anxiety. The purpose of this study is to investigate the effect of Citrus a...Anxiety is a very common mental disorder among neurological diseases. Some herbs have soothing effects and play an important role in reducing anxiety. The purpose of this study is to investigate the effect of Citrus aurantium L. essential oil on anxiety and its interference with serotonergic pathway. Sixty male mice were assigned into control, sham (saline and olive oil), and experimental groups. Intraperitoneal injection of Citrus aurantium L. essential oil was applied at doses of 0.5, 2.5, and 5 percent for 5 days. In another set of experiments, after intraperitoneal injection of Citrus aurantium L. essential oil at doses of 0.5, 2.5, and 5 percent for 5 days, on the 5th day, 30 minutes before applying essential oil, fluoxetine (2 mg/kg) was injected. Then, the anxiety-related behavior was assessed using elevated plus maze test. The results revealed that injection of essential oil of Citrus aurantium L. alone or along with fluoxetine led to increasing the number of entries into the open arms and the time spent in open arms that was significantly different compared with control and sham groups (P?< 0.001). Besides, further effects revealed when fluoxetine added to essential oils, however no more effects obtained when compared to fluoxetine alone. It is concluded that Citrus aurantium L. essential oil can reduce the anxiety in male mice and due to fluoxetin potentiation and maximum response observed, the herb may express its anxiolytic effects in part, via serotonergic system.展开更多
AIM: To investigate changes in vasoactive intestinal polypeptide (VIP) and corticotrophin releasing factor (CRF) in the plasma and duodenum of chronic stress- induced depressed rats and the effects of fluoxetine hydro...AIM: To investigate changes in vasoactive intestinal polypeptide (VIP) and corticotrophin releasing factor (CRF) in the plasma and duodenum of chronic stress- induced depressed rats and the effects of fluoxetine hydrochloride (fluoxetine) treatment on depression- induced changes in VIP and CRF. METHODS: A Sprague-Dawley rat model of chronic stress-induced depression was produced. Thirty experimental rats were randomly divided into the following groups: control group, saline-treated depressed group, and fluoxetine-treated depressed group. Open- f ield testing was performed to assess the rats’ behavior. VIP and CRF levels in plasma were measured by ELISA. Immunofluorescence techniques combined with laser scanning confocal microscopy (LSCM) were used to investigate VIP and CRF expression in the duodenum. RESULTS: The open-field behavior, both crossing and rearing, of depression model rats, decreased signif icantly compared with those of normal control rats over 5 min. Defecation times increased significantly. Compared to the control group, FITC fluorescence of duodenal CRF expression and plasma CRF levels in the depressed rats increased significantly (fluorescence intensity of duodenal CRF: 11.82 ± 2.54 vs 25.17 ± 4.63; plasma CRF: 11.82 ± 2.54 ng/L vs 25.17 ± 4.63 ng/L, P < 0.01), whereas duodenal VIP expression and plasma VIP levels decreased signif icantly (fluorescence intensity of duodenal VIP: 67.37 ± 18.90 vs 44.51 ± 16.37; plasmaVIP: 67.37 ± 18.90 ng/L vs 44.51 ± 16.37 ng/L, P < 0.01). Fluoxetine improved depressed behavior, increased VIP expression and decreased CRF expression in plasma and the duodenal tissue of depressed rats. CONCLUSION: Chronic stress can induce injury to the duodenum, accompanied by increasing CRF and decreasing VIP in the plasma and duodenum. Treatment with fluoxetine can ameliorate pathological changes in the duodenum of depressed rats, which suggests that antidepressants are an effective therapeutic agent for some duodenal diseases caused by chronic stress. VIP is a potential therapeutic strategy.展开更多
BACKGROUND Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors.Long-term fluoxetine treatment results in hepatotoxicity.Baicalin,a...BACKGROUND Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors.Long-term fluoxetine treatment results in hepatotoxicity.Baicalin,a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant,hepatoprotective and anti-inflammatory effects.However,the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported.AIM To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.METHODS Male albino Wistar rats were divided into seven groups.Group 1 was the normal control.Oral fluoxetine was administered at 10 mg/kg body weight to groups 2,3,4 and 5.In addition,groups 3 and 4 were also co-administered oral baicalin(50 mg/kg and 100 mg/kg,respectively)while group 5 received silymarin(100 mg/kg),a standard hepatoprotective compound for comparison.Groups 6 and 7 were used as a positive control for baicalin(100 mg/kg)and silymarin(100 mg/kg),respectively.All treatments were carried out for 28 d.After sacrifice of the rats,biomarkers of oxidative stress[superoxide dismutase(SOD),catalase(CAT),reduced glutathione(GSH),glutathione-S-transferase(GST),advanced oxidation protein products(AOPP),malondialdehyde(MDA)],and liver injury[alanine transaminase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),total protein,albumin,bilirubin]were studied in serum and tissue using standard protocols and diagnostic kits.Inflammatory markers[tumor necrosis factor(TNF-α),interleukin(IL)-6,IL-10 and interferon(IFN)-γ]in serum were evaluated using ELISA-based kits.The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections.RESULTS Fluoxetine-treated rats showed elevated levels of the serum liver function markers(total bilirubin,ALT,AST,and ALP)and inflammatory markers(TNF-α,IL-6,IL-10 and IFN-γ),with a decline in total protein and albumin levels.Biochemical markers of oxidative stress such as SOD,CAT,GST,GSH,MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage.Histological examination of liver tissue also showed degeneration of hepatocytes.Concurrent administration of baicalin(50 and 100 mg/kg)restored the biomarkers of oxidative stress,inflammation and hepatic damage in serum as well as in liver tissues to near normal levels.CONCLUSION These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage.Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.展开更多
BACKGROUND Major depressive disorder(MDD)is a global health issue that affects 350 million people of all ages.Although between 2%and 5.6%of affected individuals are adolescents,research on young patients is limited.Th...BACKGROUND Major depressive disorder(MDD)is a global health issue that affects 350 million people of all ages.Although between 2%and 5.6%of affected individuals are adolescents,research on young patients is limited.The inflammatory response contributes to the onset of depression,and in adult MDD patients,symptom severity has been linked to chemokine levels.AIM To determine the differences in circulatory levels of chemokines in healthy volunteers(HVs)and adolescents with MDD,and assess the changes induced by fluoxetine consume.METHODS The 22 adolescents with MDD were monitored during the first 8 wk of clinical follow-up and clinical psychiatric evaluation was done using the Hamilton depresión rating scale(HDRS).The serum levels of monocyte chemoattractant protein-1(MCP-1),macrophage inflammatory protein(MIP)-1α,MIP-1β,interleukin(IL)-8,interferon gamma-induced protein(IP)-10,and eotaxin were measured in patients and HVs.RESULTS In all cases,significant differences were detected in circulating chemokine levels between patients before treatment and HVs(P<0.0001).All chemokines decreased at 4 wk,but only MCP-1 and IL-8 significantly differed(P<0.05)between 0 wk and 4 wk.In the patients,all chemokines rose to their initial concentrations by 8 wk vs 0 wk,but only IP-10 did so significantly(P<0.05).All patients experienced a significant decrease in HDRS scores at 4 wk(P<0.0001)and 8 wk(P<0.0001)compared with 0 wk.CONCLUSION Despite the consumption of fluoxetine,patients had significantly higher chemokine levels,even after considering the improvement in HDRS score.The high levels of eotaxin,IP-10,and IL-8 partially explain certain aspects that are affected in MDD such as cognition,memory,and learning.展开更多
OBJECTIVE: To investigate the effects of Sini San and fluoxetine on the levels of central and peripheral 5-HT in a rat model of depression, and provide new insight into the treatment of depression with integrated Chin...OBJECTIVE: To investigate the effects of Sini San and fluoxetine on the levels of central and peripheral 5-HT in a rat model of depression, and provide new insight into the treatment of depression with integrated Chinese-Western Medicine.METHODS: A rat model of depression was established by chronic mild stress(CMS). Model rats received either Sini San, fluoxetine, a combination of the two drugs, or no drug treatment. Healthy naive rats were used as controls. Open field and sucrose preference tests were used to assess depression-like behavior. ELISA and immunohistochemistry were used to determine central and peripheral levels of 5-HT.RESULTS: In the group with no drug treatment,central 5-HT expression decreased while peripheral5-HT concentrations increased as CMS continued.Four weeks after CMS, Sini San alone was less effective in reducing depression-like behavior than fluoxetine alone or in combination with Sini San,but combined use was more effective than fluoxetine alone. Eight weeks after CMS, Sini San alone or in combination with fluoxetine was more effective in reducing depression-like behavior than fluoxetine alone. Furthermore Sini San and fluoxetine used alone or in combination notably increased central 5-HT expression and decreased peripheral 5-HT levels in the rat model.CONCLUSION:The results of the present study indicate that there is a synergistic action between the two medicines in the treatment of depression. Sini San exhibited a relatively long lag before its effects were observed; however, by eight weeks the Traditional Chinese Medicine appeared at least as effective as fluoxetine. We suggest that Sini San can replace fluoxetine in the later stages of depression treatment to minimize side effects observed with long-term fluoxetine administration.展开更多
Fluoxetine(Prozac^(TM))is the only antidepressant approved by the US Food and Drug Administration(FDA)for the treatment of major depressive disorder(MDD)in children.Despite its considerable efficacy as a selective ser...Fluoxetine(Prozac^(TM))is the only antidepressant approved by the US Food and Drug Administration(FDA)for the treatment of major depressive disorder(MDD)in children.Despite its considerable efficacy as a selective serotonin reuptake inhibitor,the possible long-term effects of fluoxetine on brain development in children are poorly understood.In the current study,we aimed to delineate molecular mechanisms and protein biomarkers in the brains of juvenile rhesus macaques(Macaca mulatta)one year after the discontinuation of fluoxetine treatment using proteomic and phosphoproteomic profiling.We identified several differences in protein expression and phosphorylation in the dorsolateral prefrontal cortex(DLPFC)and cingulate cortex(CC)that correlated with impulsivity in animals,suggesting that the GABAergic synapse pathway may be affected by fluoxetine treatment.Biomarkers in combination with the identified pathways contribute to a better understanding of the mechanisms underlying the chronic effects of fluoxetine after discontinuation in children.展开更多
AIM: To investigate the effects of fluoxetine on depression-induced changes of mast cell morphology and protease-1 (rMCP-1) expression in rats. METHODS: A Sprague-Dawley rat model of chronic stress-induced depression ...AIM: To investigate the effects of fluoxetine on depression-induced changes of mast cell morphology and protease-1 (rMCP-1) expression in rats. METHODS: A Sprague-Dawley rat model of chronic stress-induced depression was established. Fifty experimental rats were randomly divided into the following groups: normal control group, fluoxetine + normal control group, depressed model group, saline + depressed model group, and fluoxetine + depressed model group. Laser scanning confocal microscopy (LSCM) immunofluorecence and RT-PCR techniques were used to investigate rMCP-1 expression in gastric antrum. Mast cell morphology was observed under transmission electron microscopy. ANOVA was used for statistical analysis among groups.RESULTS: Morphologic observation indicated that depression induced mast cell proliferation, activation, and granule hyperplasia. Compared with the normal control group, the average immunofluorescence intensity of gastric antrum rMCP-1 significantly increased in depressed model group (37.4 ± 7.7 vs 24.5 ± 5.6, P < 0.01) or saline + depressed model group (39.9 ± 5.0 vs 24.5 ± 5.6, P < 0.01), while there was no significant difference between fluoxetine + normal control group (23.1 ± 3.4) or fluoxetine + depressed model group (26.1 ± 3.6) and normal control group.The average level of rMCP-1mRNA of gastric antrum significantly increased in depressed model group (0.759 ± 0.357 vs 0.476 ± 0.029, P < 0.01) or saline + depressed model group (0.781 ± 0.451 vs 0.476 ± 0.029, P < 0.01 ), while no significant difference was found between fluoxetine + normal control group (0.460 ± 0.027) or fluoxetine + depressed model group (0.488 ± 0.030) and normal control group. Fluoxetine showed partial inhibitive effects on mast cell ultrastructural alterations and de-regulated rMCP-1 expression in gastric antrum of the depressed rat model.CONCLUSION: Chronic stress can induce mast cell proliferation, activation, and granule hyperplasia in gastric antrum. Fluoxetine counteracts such changes in the depressed rat model.展开更多
AIM: To investigate the mechanism of action of lipophilic antidepressant fluoxetine(FLX) in representative molecular subtypes of breast cancer.METHODS: The anti-proliferative effects and mechanistic action of FLX in t...AIM: To investigate the mechanism of action of lipophilic antidepressant fluoxetine(FLX) in representative molecular subtypes of breast cancer.METHODS: The anti-proliferative effects and mechanistic action of FLX in triple-negative(SUM149PT) and luminal(T47D and Au565) cancer cells and nontransformed MCF10 A were investigated. Reverse phase protein microarray(RPPM) was performed with and without 10 μmol/L FLX for 24 and 48 h to determine which proteins are significantly changed. Viability and cell cycle analysis were also performed to determine drug effects on cell growth. Western blotting was used to confirm the change in protein expression examined by RPPM or pursue other signaling proteins. RESULTS: The FLX-induced cell growth inhibition in all cell lines was concentration- and time-dependent but less pronounced in early passage MCF10 A. In comparison to the other lines,cell growth reduction in SUM149 PT coincided with significant induction of endoplasmic reticulum(ER) stress and autophagy after 24 and 48 h of 10 μmol/L FLX,resulting in decreased translation of proteins along the receptor tyrosine kinase/Akt/mammalian target of rapamycin pathways. The increase in autophagy marker,cleaved microtubule-associated protein 1 light chain 3,in SUM149 PT after 24 h of FLX was likely due to increased metabolic demands of rapidly dividing cells and ER stress. Consequently,the unfolded protein response mediated by double-stranded RNA-dependent protein kinase-like ER kinase resulted in inhibition of protein synthesis,growth arrest at the G1 phase,autophagy,and caspase-7-mediated cell death.CONCLUSION: Our study suggests a new role for FLX as an inducer of ER stress and autophagy,resulting in death of aggressive triple negative breast cancer SUM149 PT.展开更多
基金Supported by the Suzhou Science and Technology Bureau(No.SKY2023175)the Project of State Key Laboratory of Radiation Medicine and Protection+6 种基金Soochow University(No.GZK1202309)the Advantage Subject Lifting Project(No.XKTJ-XK202412)the Suzhou Science and Education for Strengthening Healthcare(No.MSXM2024010)the Suzhou Medical Key Supported Disciplines(No.SZFCXK202118)the Youth Scientific Research Fund Project of Kunshan Hospital of Traditional Chinese Medicine(No.2024QNJJ06)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.SJCX23_1673)the Undergraduate Training Program for Innovation and Entrepreneurship,Soochow University(No.202310285162Y).
文摘AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the regulatory effects of fluoxetine(FLX)treatment and binocular form deprivation(BFD)on these indices.METHODS:Wistar rats were assigned to three experimental cohorts:1)Age-related groups:postnatal week(PW)1,PW3,PW5,PW7,and PW9;2)FLX treatment duration groups:FLX 0W,FLX 2W,FLX 4W,FLX 6W,and FLX 8W;3)Intervention groups:control(Cont),FLX,BFD,and BFD+FLX.The levels of PNNs,PV,and PNNs/PV coexpression in the visual cortex were detected and analyzed.RESULTS:The density of PV-positive cells and the coexpression of PNNs and PV increased gradually with the maturation of the visual cortex(b=0.960,P<0.01).The ratio of PV-positive cells surrounded by PNNs to total PV-positive cells(PNNs+/PV+/total PV+)was significantly decreased in the FLX 4W group(χ^(2)=9.03,P=0.003).There was no significant difference in the PNNs+/PV+/total PV+ratio between the FLX and BFD groups(χ^(2)=1.08,P=0.161),but a significant difference was observed between the BFD+FLX group and the BFD group(χ^(2)=5.82,P<0.01).CONCLUSION:The number of PV-positive neurons and PNNs-surrounded PV neurons in the rat visual cortex increases postnatally and reaches adult levels by postnatal week 7.Chronic FLX treatment downregulates these expressions.Combined 4-week FLX treatment and BFD exerts a more significant inhibitory effect on the PNNs+/PV+/total PV+ratio than either intervention alone.
基金Supported by the General Program of Shanghai Science and Technology Commission on Medical Innovation Research,No.21Y11923500the Second Round of the“National Medical Strong and Excellent”Three-Year Action Plan(2022-2024)of the Hongkou District of Shanghai Traditional Chinese Medicine Schools and Characteristic Technology Inheritance Support Construction Project,No.HKGYQYXM-2022-17the Shanghai Culture and Tourism Bureau.
文摘BACKGROUND Depression is a common,chronic,and recurrent mood disorder that has become a worldwide health hazard.Fluoxetine hydrochloride,a common treatment method,can inhibit 5-hydroxytryptamine(5-HT)recycling in the presynaptic membrane;however,the efficacy of a single drug is inadequate.At present,mildto-moderate depression can be treated with acupuncture of ghost caves,but the clinical curative effect of combined therapy with fluoxetine hydrochloride has not been sufficiently reported.AIM To evaluate the clinical effect of acupuncture at ghost points combined with fluoxetine hydrochloride in the treatment of mild-to-moderate depression.METHODS This retrospective study included 160 patients with mild-to-moderate depression who were admitted to Shanghai Hospital of Integrated Traditional Chinese and Western Medicine,Affiliated to Shanghai University of Traditional Chinese Medicine,between January 2022 and June 2023.Patients were separated into a single-agent group(fluoxetine hydrochloride treatment,n=80)and a coalition group(fluoxetine hydrochloride treatment combined with acupuncture at ghost points,n=80).Pre-treatment symptoms were recorded,and the clinical curative effect and adverse reactions[Asberg Antidepressant Side Effects Scale(SERS)]were assessed.Depression before and after treatment[Hamilton Depression Scale(HAMD)-24],neurotransmitter levels[5-HT,norepinephrine(NE),dopamine(DA)],oxidative stress indicators[superoxide dismutase(SOD),malondialdehyde(MDA)],and sleep quality[Pittsburgh Sleep Quality Index(PSQI)]were compared.RESULTS The total efficacy rate was 97.50%in the coalition group and 86.25%in the single-agent group(P<0.05).After 2,4,6,and 8 wk of treatment,the HAMD,self-rating depression scale,and SERS scores of the coalition and single-agent groups decreased compared with pre-treatment,and the decrease was more significant in the coalition group(P<0.05).After 8 wk of treatment,the levels of NE,DA,5-HT,and SOD in the coalition and single-agent groups increased,while the levels of MDA decreased;the increases and decrease in the coalition group were more significant(P<0.05).The PSQI scores of the coalition and single-agent groups decreased,and the decrease was more significant in the coalition group(P<0.05).CONCLUSION Acupuncture at ghost points combined with paroxetine tablets can safely improve depressive symptoms and sleep disorders,regulate neurotransmitter levels,and reduce stress responses in patients with mild-to-moderate depression.
基金supported by grants from the National Nature Science Foundation of China(32271034,32070964,82301703,32300791,and 81901378)Science and Technology Innovation Enhancement Project of Army Medical University(2022XQN40)+4 种基金National Key Research and Development Program of China(2021ZD0201703)Chongqing Natural Science Fund for Distinguished Young Scholars(CSTB2023NSCQ-JQX0030)Undergraduate Research Cultivation Project of Army Medical University(2020XBK16)Guangdong Basic and Applied Basic Research Foundation(2021A1515110268 and 2023A1515010651)Shenzhen Fundamental Research Program(RCBS20210706092411028 and JCYJ20210324121214039).
文摘Posttraumatic stress disorder(PTSD)is a complex mental disorder notable for traumatic experience memory.Although current first-line treatments are linked with clinically important symptom reduction,a large proportion of patients retained to experience considerable residual symptoms,indicating pathogenic mechanism should be illustrated further.Recent studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory preservation.However,its role in PTSD remains to be elucidated.In this study,we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and hippocampus.Fluoxetine,but not risperidone or sertraline,has a more profound rescue effect on neuropsychological behaviors and myelin abnormalities.Further mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt signaling.Our data demonstrated the correlation between PTSD and abnormal myelination,suggesting that the oligodendroglial lineage could be a target for PTSD treatment.
基金supported by the National Natural Science Foundation of China(No.41601519)。
文摘The frequent detection of pharmaceutical compounds in the environment has led to a growing awareness,which may pose a major threat to the aquatic environment.In this study,photodegradation(direct and indirect photolysis)of two different dissociation states of fluoxetine(FLU)was investigated in water,mainly including the determination of photolytic transition states and products,and the mechanisms of indirect photodegradation with·OH,CO_(3)^(*-)and NO_(3)^(*).The main direct photolysis pathways are defluorination and C–C bond cleavage.In addition,the indirect photodegradation of FLU in water is mainly through the reactions with·OH and NO_(3)^(*),and the photodegradation reaction with CO_(3)^(*-)is relatively difficult to occur in the water environment.Our results provide a theoretical basis for understanding the phototransformation process of FLU in the water environment and assessing its potential risk.
文摘Although depression may affect patients＇ recovery and even their survival rate after stroke,it is often overlooked or inadequately managed.And data regarding the treatment efficacy and safety of fluoxetine in this setting are inconsistent.We aimed to systematically assess those two indices in patients with post-stroke depression （PSD）.Through a systematic literature search in 10 biomedical databases,244 articles were first identified,through which we collected and evaluated a total of 600 patients identified from 11 RCTs.The meta-analysis with Revman software indicated that fluoxetine was more effective than placebo,the combined results of 9 RCTs showed that fluoxetine decreased the depression rating scale scores significantly compared with placebo,and the pooled weighted mean difference （WMD） was 0.44 （95% CI-0.03 to 0.92）.Moreover,time-dependent effects were also observed.No consistent evidence was found for its positive effects on the recovery of neurological impairments and improvements in activities of daily living （ADL）.Six studies reported rate of adverse effects in both fluoxetine groups and control groups and showed no significant difference between them （OR=0.03,95% CI-0.00 to 0.07）.This meta-analysis suggested that fluoxetine may be effective and safe for patients with PSD and it may have time-dependent effects.
基金supported by the National Natural Science Foundation of China(81471369)Innovative Experiments on Physiology of Zhejiang University School of Medicine
文摘Depression is a debilitating psychiatric disorder with a huge socioeconomic burden, and its treatment relies on antidepressants including selective serotonin reuptake inhibitors(SSRIs). Recently, the melatonergic system that is closely associated with the serotonergic system has been implicated in the pathophysiology and treatment of depression. However, it remains unknown whether combined treatment with SSRI and melatonin has synergistic antidepressant effects. In this study, we applied a sub-chronic restraint stress paradigm, and evaluated the potential antidepressant effects of combined fluoxetine and melatonin in adult male mice. Sub-chronic restraint stress(6 h/day for 10 days) induced depression-like behavior as shown by deteriorated fur state, increased latency to groom in the splash test, and increased immobility time in the forced-swim test. Repeated administration of either fluoxetine or melatonin at 10 mg/kg during stress exposure failed to prevent depression-like phenotypes. However,combined treatment with fluoxetine and melatonin at theselected dose attenuated stress-induced behavioral abnormalities. Moreover, we found that the antidepressant effects of combined treatment were associated with the normalization of brain-derived neurotrophic factor(BDNF)–tropomyosin receptor kinase B(Trk B) signaling in the hippocampus, but not in the prefrontal cortex. Our findings suggest that combined fluoxetine and melatonin treatment exerts synergistic antidepressant effects possibly by restoring hippocampal BDNF–Trk B signaling.
基金Supported by program of Shanghai Municipal of Health and Family Planning,China(Clinical Standardized Study of Wrist-Ankle Acupuncture and Fluoxetine in the Treatment of Post-Stroke Depression,No.2012QL042A)Natural Science Foundation of China(Study on Mechanismof Acupuncture Protecting Neurovascular Unit from Injury in MACO Model Rats by Electroacupuncture Based on lnc-RNA,No.81503647)。
文摘OBJECTIVE: To investigate the effects of WAA combined with fluoxetine in the clinical treatment of post-stroke depression(PSD).METHODS: In this randomized, controlled and single-blind trial, 105 PSD patients who met the inclusion criteria were randomly divided into three equal groups: Thin wrist-ankle acupuncture(WAA)group(Thin WAA needle + Fluoxetine), Thick WAA group(Thick WAA needle + Fluoxetine), and Sham WAA group(sham WAA needle + Fluoxetine). In this trial, the primary outcome was Hamilton Depression Scale(HAMD), while the secondary outcomes included Zung self-rating depression scale(SDS) and World Health Organization Quality of Life BREF(QQL).RESULTS: Ninety nine PSD patients completed all the treatment. The HAMD scores and SDS scores of all the three groups decreased after treatment(P <0.05);thick WAA group and thin WAA group decreased more obviously than the sham WAA group(P < 0.05). There was no significant difference between the QQL scores of the three groups(P >0.05). There was no significant difference in the scores of the three scales between the thick wrist ankle needles and the thin wrist ankle needles(P >0.05).CONCLUSION: The present study showed that WAA combined with fluoxetine can relieve the symptoms of depression after stroke. WAA therapy could improve the antidepressant effect of fluoxetine.
基金supported by the National Natural Science Foundation of China (81601938)the Natural Science Fund of Shaanxi Province (2016JQ8010)the Science and Technology Projects Fund of Xi’an city (2016050SF/YX06(6))
文摘Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage(SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury(EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine(10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier(BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1 b, IL-6, TNF-a, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.
基金Supported by Shanghai Science and Technology Commission TCM Guidance Project,No.19401935500Shanghai University of Traditional Chinese Medicine Budget Scientific Research Project,No.2020LK079Medical Innovation Research Special General Project of Shanghai Science and Technology Commission,No.21Y11923500.
文摘BACKGROUND Depression affects more than 350 million people worldwide.In China,4.2%(54 million people)of the total population suffers from depression.Psychotherapy has been shown to change cognition,improve personality,and enhance the ability to cope with difficulties and setbacks.While pharmacotherapy can reduce symptoms,it is also associated with adverse reactions and relapse after drug withdrawal.Therefore,there has been an increasing emphasis placed on the use of non-pharmacological therapies for depression.The hypothesis of this study was that acupuncture at ghost points combined with fluoxetine would be more effective than fluoxetine alone for the treatment of depression.AIM To investigate the efficacy of acupuncture at ghost points combined with fluoxetine for the treatment of patients with depression.METHODS This randomized controlled trial included patients with mild to moderate depression(n=160).Patients received either acupuncture at ghost points combined with fluoxetine(n=80)or fluoxetine alone(control group,n=80).Needles were retained in place for 30 min,5 times a week;three treatment cycles were administered.The Mann–Whitney U test was used to compare functional magnet resonance imaging parameters,Hamilton depression rating scale(HAMD)scores,and self-rating depression scale(SDS)scores between the acupuncture group and control group.RESULTS There were no significant differences in HAMD or SDS scores between the acupuncture group and control group,before or after 4 wk of treatment.The acupuncture group exhibited significantly lower HAMD and SDS scores than the control group after 8 wk of treatment(P<0.05).The acupuncture group had significantly lower fractional Amplitude of Low Frequency Fluctuations values for the left anterior wedge leaf,left posterior cingulate gyrus,left middle occipital gyrus,and left inferior occipital gyrus after 8 wk.The acupuncture group also had significantly higher values for the right inferior frontal gyrus,right insula,and right hippocampus(P<0.05).After 8 wk of treatment,the effective rates of the acupuncture and control groups were 51.25%and 36.25%,respectively(P<0.05).CONCLUSION The study results suggest that acupuncture at ghost points combined with fluoxetine is more effective than fluoxetine alone for the treatment of patients with mild to moderate depression.
基金This work was supported by the Scientific Research Projects of Universities in Inner Mongolia Autonomous Region(NJZY111)Natural Scientific Research Projects of Inner Mongolia Autonomous Region(2020MS03060)We thank Elsevier Ltd.,UK and FreeScience,China for their assistance in English editing of the manuscript.
文摘Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity.The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise.Recent studies have demonstrated that altered expressions of long non-coding RNAs(lncRNAs)in the brain affect neurodevelopment and manifest modulating functions during the depression.However,most lncRNAs have not yet been studied.Herein,we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors,as well as their corresponding response following antidepressant fluoxetine treatment.A chronic unpredictable mild stress(CUMS)mouse model was applied.A sixweek fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors.In addition,differential expression analysis of lncRNAs was performed following RNA-sequencing.A total of 282 lncRNAs(134 up-regulated and 148 down-regulated)were differentially expressed in CUMS-induced mice relative to non-stressed counterparts(P<0.05).Moreover,370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention.Gene Ontology(GO)analyses showed an association between significantly dysregulated lncRNAs and protein binding,oxygen binding,and transport activity,while the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways.Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus.The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.
文摘Objective: This study is to investigate the clinical therapeutic effects and safety of treating mild or moderate depression with somatic symptoms with electroacupuncture combined with Fluoxetine. Methods: 95 cases of mild or moderate depression with somatic symptoms were randomly divided into a Fluoxetine group, and an electroacupuncture plus Fluoxetine group. Hamilton Depression Scale (HAMD) was used for the assessment of clinical therapeutic effects and Treatment Emergent Symptom Scale (TESS) was used for assessment of adverse reactions. Results: The total effective rate was 77.27% in the Fluoxetine group and 78.26% in the electroacupuncture plus Fluoxetine group, showing no statistically significant difference between these two groups (P>0.05). However, the treatment took effect after two weeks in the electroacupuncture plus Fluoxetine group but after four weeks in Fluoxetine group. During this time, a better therapeutic effect on depression with mild or moderate somatic symptoms was found in the electroacupuncture plus Fluoxetine group, which also had fewer adverse reactions than the Fluoxetine group. Conclusion: Electroacupuncture combined with Fluoxetine takes effect faster for relieving the somatic symptoms with fewer adverse reactions. It is worth popularizing clinically.
文摘Anxiety is a very common mental disorder among neurological diseases. Some herbs have soothing effects and play an important role in reducing anxiety. The purpose of this study is to investigate the effect of Citrus aurantium L. essential oil on anxiety and its interference with serotonergic pathway. Sixty male mice were assigned into control, sham (saline and olive oil), and experimental groups. Intraperitoneal injection of Citrus aurantium L. essential oil was applied at doses of 0.5, 2.5, and 5 percent for 5 days. In another set of experiments, after intraperitoneal injection of Citrus aurantium L. essential oil at doses of 0.5, 2.5, and 5 percent for 5 days, on the 5th day, 30 minutes before applying essential oil, fluoxetine (2 mg/kg) was injected. Then, the anxiety-related behavior was assessed using elevated plus maze test. The results revealed that injection of essential oil of Citrus aurantium L. alone or along with fluoxetine led to increasing the number of entries into the open arms and the time spent in open arms that was significantly different compared with control and sham groups (P?< 0.001). Besides, further effects revealed when fluoxetine added to essential oils, however no more effects obtained when compared to fluoxetine alone. It is concluded that Citrus aurantium L. essential oil can reduce the anxiety in male mice and due to fluoxetin potentiation and maximum response observed, the herb may express its anxiolytic effects in part, via serotonergic system.
基金Supported by Department of Mental Health Center andDepartment Gastroenterology of Renmin Hospital of WuhanUniversity, Hubei Province, China
文摘AIM: To investigate changes in vasoactive intestinal polypeptide (VIP) and corticotrophin releasing factor (CRF) in the plasma and duodenum of chronic stress- induced depressed rats and the effects of fluoxetine hydrochloride (fluoxetine) treatment on depression- induced changes in VIP and CRF. METHODS: A Sprague-Dawley rat model of chronic stress-induced depression was produced. Thirty experimental rats were randomly divided into the following groups: control group, saline-treated depressed group, and fluoxetine-treated depressed group. Open- f ield testing was performed to assess the rats’ behavior. VIP and CRF levels in plasma were measured by ELISA. Immunofluorescence techniques combined with laser scanning confocal microscopy (LSCM) were used to investigate VIP and CRF expression in the duodenum. RESULTS: The open-field behavior, both crossing and rearing, of depression model rats, decreased signif icantly compared with those of normal control rats over 5 min. Defecation times increased significantly. Compared to the control group, FITC fluorescence of duodenal CRF expression and plasma CRF levels in the depressed rats increased significantly (fluorescence intensity of duodenal CRF: 11.82 ± 2.54 vs 25.17 ± 4.63; plasma CRF: 11.82 ± 2.54 ng/L vs 25.17 ± 4.63 ng/L, P < 0.01), whereas duodenal VIP expression and plasma VIP levels decreased signif icantly (fluorescence intensity of duodenal VIP: 67.37 ± 18.90 vs 44.51 ± 16.37; plasmaVIP: 67.37 ± 18.90 ng/L vs 44.51 ± 16.37 ng/L, P < 0.01). Fluoxetine improved depressed behavior, increased VIP expression and decreased CRF expression in plasma and the duodenal tissue of depressed rats. CONCLUSION: Chronic stress can induce injury to the duodenum, accompanied by increasing CRF and decreasing VIP in the plasma and duodenum. Treatment with fluoxetine can ameliorate pathological changes in the duodenum of depressed rats, which suggests that antidepressants are an effective therapeutic agent for some duodenal diseases caused by chronic stress. VIP is a potential therapeutic strategy.
基金financial support from University Grants Commission, New Delhi, India in the form of UGC-Junior Research Fellowship and Senior Research Fellowshipfinancial support from Council of Scientific & Industrial Research, New Delhi, India in the form of CSIR Junior Research Fellowship and Senior Research Fellowship
文摘BACKGROUND Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors.Long-term fluoxetine treatment results in hepatotoxicity.Baicalin,a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant,hepatoprotective and anti-inflammatory effects.However,the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported.AIM To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.METHODS Male albino Wistar rats were divided into seven groups.Group 1 was the normal control.Oral fluoxetine was administered at 10 mg/kg body weight to groups 2,3,4 and 5.In addition,groups 3 and 4 were also co-administered oral baicalin(50 mg/kg and 100 mg/kg,respectively)while group 5 received silymarin(100 mg/kg),a standard hepatoprotective compound for comparison.Groups 6 and 7 were used as a positive control for baicalin(100 mg/kg)and silymarin(100 mg/kg),respectively.All treatments were carried out for 28 d.After sacrifice of the rats,biomarkers of oxidative stress[superoxide dismutase(SOD),catalase(CAT),reduced glutathione(GSH),glutathione-S-transferase(GST),advanced oxidation protein products(AOPP),malondialdehyde(MDA)],and liver injury[alanine transaminase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),total protein,albumin,bilirubin]were studied in serum and tissue using standard protocols and diagnostic kits.Inflammatory markers[tumor necrosis factor(TNF-α),interleukin(IL)-6,IL-10 and interferon(IFN)-γ]in serum were evaluated using ELISA-based kits.The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections.RESULTS Fluoxetine-treated rats showed elevated levels of the serum liver function markers(total bilirubin,ALT,AST,and ALP)and inflammatory markers(TNF-α,IL-6,IL-10 and IFN-γ),with a decline in total protein and albumin levels.Biochemical markers of oxidative stress such as SOD,CAT,GST,GSH,MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage.Histological examination of liver tissue also showed degeneration of hepatocytes.Concurrent administration of baicalin(50 and 100 mg/kg)restored the biomarkers of oxidative stress,inflammation and hepatic damage in serum as well as in liver tissues to near normal levels.CONCLUSION These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage.Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.
基金Secretaria de Ciencia,Tecnología e Innovación,No.0048/2014。
文摘BACKGROUND Major depressive disorder(MDD)is a global health issue that affects 350 million people of all ages.Although between 2%and 5.6%of affected individuals are adolescents,research on young patients is limited.The inflammatory response contributes to the onset of depression,and in adult MDD patients,symptom severity has been linked to chemokine levels.AIM To determine the differences in circulatory levels of chemokines in healthy volunteers(HVs)and adolescents with MDD,and assess the changes induced by fluoxetine consume.METHODS The 22 adolescents with MDD were monitored during the first 8 wk of clinical follow-up and clinical psychiatric evaluation was done using the Hamilton depresión rating scale(HDRS).The serum levels of monocyte chemoattractant protein-1(MCP-1),macrophage inflammatory protein(MIP)-1α,MIP-1β,interleukin(IL)-8,interferon gamma-induced protein(IP)-10,and eotaxin were measured in patients and HVs.RESULTS In all cases,significant differences were detected in circulating chemokine levels between patients before treatment and HVs(P<0.0001).All chemokines decreased at 4 wk,but only MCP-1 and IL-8 significantly differed(P<0.05)between 0 wk and 4 wk.In the patients,all chemokines rose to their initial concentrations by 8 wk vs 0 wk,but only IP-10 did so significantly(P<0.05).All patients experienced a significant decrease in HDRS scores at 4 wk(P<0.0001)and 8 wk(P<0.0001)compared with 0 wk.CONCLUSION Despite the consumption of fluoxetine,patients had significantly higher chemokine levels,even after considering the improvement in HDRS score.The high levels of eotaxin,IP-10,and IL-8 partially explain certain aspects that are affected in MDD such as cognition,memory,and learning.
基金Supported by a Grant from the National Basic Research Program of China(973 Program No.2011CB505106)
文摘OBJECTIVE: To investigate the effects of Sini San and fluoxetine on the levels of central and peripheral 5-HT in a rat model of depression, and provide new insight into the treatment of depression with integrated Chinese-Western Medicine.METHODS: A rat model of depression was established by chronic mild stress(CMS). Model rats received either Sini San, fluoxetine, a combination of the two drugs, or no drug treatment. Healthy naive rats were used as controls. Open field and sucrose preference tests were used to assess depression-like behavior. ELISA and immunohistochemistry were used to determine central and peripheral levels of 5-HT.RESULTS: In the group with no drug treatment,central 5-HT expression decreased while peripheral5-HT concentrations increased as CMS continued.Four weeks after CMS, Sini San alone was less effective in reducing depression-like behavior than fluoxetine alone or in combination with Sini San,but combined use was more effective than fluoxetine alone. Eight weeks after CMS, Sini San alone or in combination with fluoxetine was more effective in reducing depression-like behavior than fluoxetine alone. Furthermore Sini San and fluoxetine used alone or in combination notably increased central 5-HT expression and decreased peripheral 5-HT levels in the rat model.CONCLUSION:The results of the present study indicate that there is a synergistic action between the two medicines in the treatment of depression. Sini San exhibited a relatively long lag before its effects were observed; however, by eight weeks the Traditional Chinese Medicine appeared at least as effective as fluoxetine. We suggest that Sini San can replace fluoxetine in the later stages of depression treatment to minimize side effects observed with long-term fluoxetine administration.
基金supported by the Max Planck Society to C.W.T.and National Institutes of Health USDHHS(R01-HD065826to M.G.,OD011107 to Harris Lewin)。
文摘Fluoxetine(Prozac^(TM))is the only antidepressant approved by the US Food and Drug Administration(FDA)for the treatment of major depressive disorder(MDD)in children.Despite its considerable efficacy as a selective serotonin reuptake inhibitor,the possible long-term effects of fluoxetine on brain development in children are poorly understood.In the current study,we aimed to delineate molecular mechanisms and protein biomarkers in the brains of juvenile rhesus macaques(Macaca mulatta)one year after the discontinuation of fluoxetine treatment using proteomic and phosphoproteomic profiling.We identified several differences in protein expression and phosphorylation in the dorsolateral prefrontal cortex(DLPFC)and cingulate cortex(CC)that correlated with impulsivity in animals,suggesting that the GABAergic synapse pathway may be affected by fluoxetine treatment.Biomarkers in combination with the identified pathways contribute to a better understanding of the mechanisms underlying the chronic effects of fluoxetine after discontinuation in children.
文摘AIM: To investigate the effects of fluoxetine on depression-induced changes of mast cell morphology and protease-1 (rMCP-1) expression in rats. METHODS: A Sprague-Dawley rat model of chronic stress-induced depression was established. Fifty experimental rats were randomly divided into the following groups: normal control group, fluoxetine + normal control group, depressed model group, saline + depressed model group, and fluoxetine + depressed model group. Laser scanning confocal microscopy (LSCM) immunofluorecence and RT-PCR techniques were used to investigate rMCP-1 expression in gastric antrum. Mast cell morphology was observed under transmission electron microscopy. ANOVA was used for statistical analysis among groups.RESULTS: Morphologic observation indicated that depression induced mast cell proliferation, activation, and granule hyperplasia. Compared with the normal control group, the average immunofluorescence intensity of gastric antrum rMCP-1 significantly increased in depressed model group (37.4 ± 7.7 vs 24.5 ± 5.6, P < 0.01) or saline + depressed model group (39.9 ± 5.0 vs 24.5 ± 5.6, P < 0.01), while there was no significant difference between fluoxetine + normal control group (23.1 ± 3.4) or fluoxetine + depressed model group (26.1 ± 3.6) and normal control group.The average level of rMCP-1mRNA of gastric antrum significantly increased in depressed model group (0.759 ± 0.357 vs 0.476 ± 0.029, P < 0.01) or saline + depressed model group (0.781 ± 0.451 vs 0.476 ± 0.029, P < 0.01 ), while no significant difference was found between fluoxetine + normal control group (0.460 ± 0.027) or fluoxetine + depressed model group (0.488 ± 0.030) and normal control group. Fluoxetine showed partial inhibitive effects on mast cell ultrastructural alterations and de-regulated rMCP-1 expression in gastric antrum of the depressed rat model.CONCLUSION: Chronic stress can induce mast cell proliferation, activation, and granule hyperplasia in gastric antrum. Fluoxetine counteracts such changes in the depressed rat model.
基金Supported by Susan G.Komen for the Cure Career Catalyst in Disparities Research to Ibarra Drendall C(KG090730)Promise Grant to Yu D(KG091020)National Institute of Health to Seewaldt V(R01CA158668)
文摘AIM: To investigate the mechanism of action of lipophilic antidepressant fluoxetine(FLX) in representative molecular subtypes of breast cancer.METHODS: The anti-proliferative effects and mechanistic action of FLX in triple-negative(SUM149PT) and luminal(T47D and Au565) cancer cells and nontransformed MCF10 A were investigated. Reverse phase protein microarray(RPPM) was performed with and without 10 μmol/L FLX for 24 and 48 h to determine which proteins are significantly changed. Viability and cell cycle analysis were also performed to determine drug effects on cell growth. Western blotting was used to confirm the change in protein expression examined by RPPM or pursue other signaling proteins. RESULTS: The FLX-induced cell growth inhibition in all cell lines was concentration- and time-dependent but less pronounced in early passage MCF10 A. In comparison to the other lines,cell growth reduction in SUM149 PT coincided with significant induction of endoplasmic reticulum(ER) stress and autophagy after 24 and 48 h of 10 μmol/L FLX,resulting in decreased translation of proteins along the receptor tyrosine kinase/Akt/mammalian target of rapamycin pathways. The increase in autophagy marker,cleaved microtubule-associated protein 1 light chain 3,in SUM149 PT after 24 h of FLX was likely due to increased metabolic demands of rapidly dividing cells and ER stress. Consequently,the unfolded protein response mediated by double-stranded RNA-dependent protein kinase-like ER kinase resulted in inhibition of protein synthesis,growth arrest at the G1 phase,autophagy,and caspase-7-mediated cell death.CONCLUSION: Our study suggests a new role for FLX as an inducer of ER stress and autophagy,resulting in death of aggressive triple negative breast cancer SUM149 PT.
