While multiple step saccades(MSS)are occasionally reported in the healthy population,they are more evident in patients with Parkinson’s disease(PD).Therefore,MSS has been suggested as a biological marker for the diag...While multiple step saccades(MSS)are occasionally reported in the healthy population,they are more evident in patients with Parkinson’s disease(PD).Therefore,MSS has been suggested as a biological marker for the diagnosis of PD.However,the lack of clarity on the neural mechanism underlying the generation of MSS largely impedes their application in the clinic.We have proposed recently that MSS are triggered by the discrepancy between desired and executed saccades.Accordingly,brain regions involved in saccadic planning and execution might play a role in the generation of MSS.To test this hypothesis,we explored the role of the prefrontal(PFC)and posterior parietal cortex(PPC)in generating MSS by conducting two experiments:electroencephalographic recording and single-pulse transcranial magnetic stimulation in the PFC or PPC of humans while participants were performing a gap saccade task.We found that the PFC and PPC are involved in the generation of MSS.展开更多
Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connect...Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connectivity of this structure has been studied extensively over the past century,mainly using a range of anterograde and retrograde anatomical tracers[3].展开更多
Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSC...Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSCLC)and its molecular mechanism using mice bearing Lewis lung carcinoma cells.LRC significantly suppressed the growth of NSCLC.Besides,RNA sequencing of mice tumors and hematoxylin&eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes,specifically GZMB~+CD8~+T lymphocytes,in tumor tissues.The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways,suggesting that LRC exerted its effects through the PDL1/PD-1 pathway.Further experiments revealed that LRC interacted with PD-L1,blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells.Together,these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.展开更多
Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and cortex.Patients can present with a variety of symptoms that can broadly be classified into motor symptoms...Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and cortex.Patients can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive decline.The causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.展开更多
Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairme...Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.展开更多
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne...The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.展开更多
Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neu...Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neural circuit tracing.Anterograde labeling was achieved by injecting anterograde self-complementary adeno-associated viruses(scAAVs)into the IC.Retrograde tracing involved NTS injections of either retrograde scAAVs or FluoroGold(FG),combined with immunofluorescence histochemical staining to identify IC-originating projection neurons.For postsynaptic neurochemical phenotype characterization,IC was injected with AAV2/1-CaMKII-Cre,while a mixture of AAV2/9-Syn-DIO-mCherry and AAV2/9-VGAT1-EGFP was injected into the NTS.The rats were allowed to survive for one week following scAAVs or FG injection or four weeks after recombinase-dependent systems injection.Then the rats were sacrificed,and serial brain sections were prepared for immunofluorescence histochemical staining(brain section containing FG)and subsequent fluorescence/confocal microscopic analysis.Results:(1)Anterograde viral tracing re-vealed dense axonal terminals from the IC projecting to the medial subnucleus of the NTS,while retrograde tracing re-vealed that IC neurons projecting to the NTS were predominantly localized within the dysgranular layer;(2)IC-NTS projection neurons were exclusive glutamatergic(100%,n=3);(3)NTS neurons receiving IC inputs were mainly lo-calized in the medial subnucleus,and were predominantly GABAergic(79.8±3.2%,n=3).Conclusion:The pres-ent results indicate that a descending pathway from excitatory neurons of the IC terminates onto inhibitory neurons of the NTS,which might represent a potential neuromodulatory target for visceral pain disorders.展开更多
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
Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods...Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods:The PTSD mouse model was subjected to single prolonged stress and shock(SPS&S),and the animals received 15 min sessions of EA at Shenmen acupoint(HT7).Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear.Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex(PFC).Additionally,the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.Results:Mice subjected to SPS&S presented increased anxiety-and fear-like behaviors.Lcn2 expression in the PFC was significantly upregulated following SPS&S,leading to increased expression of the proinflammatory cytokines tumor necrosis factor-a and interleukin-6 and suppression of PFC neuronal activity.However,EA at HT7 inhibited Lcn2 release,reducing neuroinflammation and hypoexcitability in the PFC.Lcn2 overexpression mitigated the effects of EA at HT7,resulting in anxiety-and fear-like behaviors.Conclusion:EA at HT7 can ameliorate PTSD-associated anxiety and fear,and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC.展开更多
[Objectives]This study was conducted to investigate the alleviating effect of Phellodendri Chinensis Cortex extract on the phytotoxicity of pretilachlor in rice.[Methods]In addition to CK,Phellodendri Chinensis Cortex...[Objectives]This study was conducted to investigate the alleviating effect of Phellodendri Chinensis Cortex extract on the phytotoxicity of pretilachlor in rice.[Methods]In addition to CK,Phellodendri Chinensis Cortex extract and pretilachlor with different gradients were added to the culture medium,and rice seeds with the same bud length were evenly placed in the culture medium.After 10 and 15 d of culture,the plant height and fresh weight of rice seedlings were measured and the alleviation rate was calculated.[Results]Ten days after application,the plant height of treatment 8(pretilachlor:extract concentration ratio of 25:200)was alleviated with an alleviation rate of 21.72%,and the fresh weight of treatment 9(pretilachlor:extract concentration ratio of 25:400)was alleviated with an alleviation rate of 31.04%.Fifteen days after treatment,the plant height of treatment 6(pretilachlor:extract concentration ratio of 25:50)showed a better alleviating effect,and the fresh weight of treatment 8(pretilachlor:extract concentration ratio of 25:200)exhibited a better alleviating effect,with an alleviation rate of 22.39%.Meanwhile,it was found that the extract of Phellodendri Chinensis Cortex could alleviate the increase of POD activity in rice leaves caused by pretilachlor.Meanwhile,it was found that the extract of Phellodendri Chinensis Cortex promoted the expression of CAT in rice seedlings,thus significantly increasing its activity and alleviating the toxicity of pretilachlor to rice.[Conclusions]This study can provide technical support for the screening and field application of plant-derived safeners.展开更多
Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working...Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working memory,and emotional regulation,is notably impaired in this condition.This review consolidates current insights into the role of PFC dysfunction in schizophrenia,with a focus on its implications for therapeutic strategies.The neuroanatomical and neurobiological foundations of PFC dysfunction are explored,emphasizing structural abnormalities,functional dysconnectivity,and microcircuit disruptions that contribute to cognitive deficits and impaired decision-making.Clinical implications are discussed,particularly the correlation between PFC dysfunction and the severity and progression of schizophrenia symptoms.Additionally,pharmacological and non-pharmacological approaches aimed at modulating PFC activity are reviewed as potential therapeutic options.In conclusion,a deeper understanding of PFC dysfunction is pivotal for developing targeted treatments,and ongoing research offers promising avenues for enhancing outcomes for individuals affected by this debilitating disorder.展开更多
Within the prefrontal-cingulate cortex,abnormalities in coupling between neuronal networks can disturb the emotion-cognition interactions,contributing to the development of mental disorders such as depression.Despite ...Within the prefrontal-cingulate cortex,abnormalities in coupling between neuronal networks can disturb the emotion-cognition interactions,contributing to the development of mental disorders such as depression.Despite this understanding,the neural circuit mechanisms underlying this phenomenon remain elusive.In this study,we present a biophysical computational model encompassing three crucial regions,including the dorsolateral prefrontal cortex,subgenual anterior cingulate cortex,and ventromedial prefrontal cortex.The objective is to investigate the role of coupling relationships within the prefrontal-cingulate cortex networks in balancing emotions and cognitive processes.The numerical results confirm that coupled weights play a crucial role in the balance of emotional cognitive networks.Furthermore,our model predicts the pathogenic mechanism of depression resulting from abnormalities in the subgenual cortex,and network functionality was restored through intervention in the dorsolateral prefrontal cortex.This study utilizes computational modeling techniques to provide an insight explanation for the diagnosis and treatment of depression.展开更多
Pathological tremor is one of the cardinal symptoms in Parkinson's disease (PD).Tremor is comprised of involuntary,rhythmic,a nd oscillating movements that can vary according to the circumstances under which they ...Pathological tremor is one of the cardinal symptoms in Parkinson's disease (PD).Tremor is comprised of involuntary,rhythmic,a nd oscillating movements that can vary according to the circumstances under which they occur,the body parts that are involved,and the frequency at which they present.For example,tremors can be mild to severe,are stress sensitive,and can affect arms,legs,or the head (Dirkx and Bologna,2022).展开更多
A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex(MOC)was developed and implemented to rapidly profile and di...A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex(MOC)was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine(TCM).The strategy possessed four characteristics:1)The tailored database consisted of metabolites derived from big data-originated reference compound,metabolites predicted in silico,and MOC chemical profile-based pseudomolecular ions.2)When profiling MOC-derived metabolites in vivo,attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds,as reported by most papers,but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites.3)Metabolite traceability was performed,especially to distinguish isomeric prototypes-derived metabolites,prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds.4)Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification.Using this strategy,134 metabolites were swiftly characterized after the oral administration of MOC to rats,and several metabolites were reported for the first time.Furthermore,17 potential active metabolites were discovered by targeting the motilin,dopamine D2,and the serotonin type 4(5-HT4)receptors,and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model.This study extends the application of mass spectrometry(MS)to rapidly profile TCM-derived metabolites in vivo,which will help pharmacologists rapidly discover potent metabolites from a complex matrix.展开更多
Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivi...Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivity of basolateral amygdala(BLA)pyramidal neurons(PNs)in Shank3 InsG3680 knock-in(InsG3680+/+)mice is involved in the development of anxiety.Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs.Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+mice.Further study found that the diminished control of the BLA by medial prefrontal cortex(mPFC)and optogenetic activation of the mPFC-BLA pathway also had a rescue effect,which increased the feedforward inhibition of the BLA.Taken together,our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+mice.展开更多
Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglio...Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.展开更多
The prelimbic cortex(PL)is actively engaged in pain modulation.The infralimbic cortex(IL)has been reported to regulate the PL.However,how this regulation affects pain remains unclear.In the present study,we recorded t...The prelimbic cortex(PL)is actively engaged in pain modulation.The infralimbic cortex(IL)has been reported to regulate the PL.However,how this regulation affects pain remains unclear.In the present study,we recorded temporary hyper-activity of PL pyramidal neurons responding to nociceptive stimuli,but a temporary hypofunction of the IL by in vivo electrophysiological recording in rats with peripheral inflammation.Manipulation of the PL or IL had opposite effects on thermal hyperalgesia.Furthermore,the functional connectivity and chemogenetic regulation between the subregions indicated an inhibitory influence of the IL on the PL.Activation of the pathway from the IL to the PL alleviated thermal hyperalgesia,whereas its inhibition exacerbated chronic pain.Overall,our results suggest a new mechanism underlying the role of the medial prefrontal cortex in chronic pain:hypo-function of the IL leads to hyperactivity of the PL,which regulates thermal hyperalgesia,and thus contributes to the chronicity of pain.展开更多
Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiet...Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.展开更多
基金supported by North Sichuan Medical College(CBY23-QDA14)the National Natural Science Foundation of China(32030045 and 82071454)+4 种基金Nanchong Federation of Social Science Associations(NC24C145)the Sichuan Science and Technology Program(2024NSFSC2017,2024ZYD0086)the Sichuan Students'Platform for Innovation Training Program(S202410634035)the Health Commission of Sichuan Province(24WSXT044)funded by the Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning(CNLYB2403).
文摘While multiple step saccades(MSS)are occasionally reported in the healthy population,they are more evident in patients with Parkinson’s disease(PD).Therefore,MSS has been suggested as a biological marker for the diagnosis of PD.However,the lack of clarity on the neural mechanism underlying the generation of MSS largely impedes their application in the clinic.We have proposed recently that MSS are triggered by the discrepancy between desired and executed saccades.Accordingly,brain regions involved in saccadic planning and execution might play a role in the generation of MSS.To test this hypothesis,we explored the role of the prefrontal(PFC)and posterior parietal cortex(PPC)in generating MSS by conducting two experiments:electroencephalographic recording and single-pulse transcranial magnetic stimulation in the PFC or PPC of humans while participants were performing a gap saccade task.We found that the PFC and PPC are involved in the generation of MSS.
文摘Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connectivity of this structure has been studied extensively over the past century,mainly using a range of anterograde and retrograde anatomical tracers[3].
基金supported by Natural Science Foundation of Guangdong Province,China(2022A1515011575)National Natural Science Foundation of China,China(81873154)President Foundation of Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,China(1202103010)。
文摘Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSCLC)and its molecular mechanism using mice bearing Lewis lung carcinoma cells.LRC significantly suppressed the growth of NSCLC.Besides,RNA sequencing of mice tumors and hematoxylin&eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes,specifically GZMB~+CD8~+T lymphocytes,in tumor tissues.The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways,suggesting that LRC exerted its effects through the PDL1/PD-1 pathway.Further experiments revealed that LRC interacted with PD-L1,blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells.Together,these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.
文摘Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and cortex.Patients can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive decline.The causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.
基金supported by the National Natural Science Foundation of China,Nos.82374561(to JD),82174490(to JF)the Medical and Health Science and Technology Program of Zhejiang Province,No.2021RC098(to JD)the Research Project of Zhejiang Chinese Medical University,Nos.2022JKZKTS44(to JD),2022FSYYZZ07(to JF).
文摘Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.
基金supported by the National Natural Science Foundation of China,Nos.82272171(to ZY),82271403(to XL),81941011(to XL),31971279(to ZY),31730030(to XL)the Natural Science Foundation of Beijing,No.7222004(to HD).
文摘The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.
文摘Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neural circuit tracing.Anterograde labeling was achieved by injecting anterograde self-complementary adeno-associated viruses(scAAVs)into the IC.Retrograde tracing involved NTS injections of either retrograde scAAVs or FluoroGold(FG),combined with immunofluorescence histochemical staining to identify IC-originating projection neurons.For postsynaptic neurochemical phenotype characterization,IC was injected with AAV2/1-CaMKII-Cre,while a mixture of AAV2/9-Syn-DIO-mCherry and AAV2/9-VGAT1-EGFP was injected into the NTS.The rats were allowed to survive for one week following scAAVs or FG injection or four weeks after recombinase-dependent systems injection.Then the rats were sacrificed,and serial brain sections were prepared for immunofluorescence histochemical staining(brain section containing FG)and subsequent fluorescence/confocal microscopic analysis.Results:(1)Anterograde viral tracing re-vealed dense axonal terminals from the IC projecting to the medial subnucleus of the NTS,while retrograde tracing re-vealed that IC neurons projecting to the NTS were predominantly localized within the dysgranular layer;(2)IC-NTS projection neurons were exclusive glutamatergic(100%,n=3);(3)NTS neurons receiving IC inputs were mainly lo-calized in the medial subnucleus,and were predominantly GABAergic(79.8±3.2%,n=3).Conclusion:The pres-ent results indicate that a descending pathway from excitatory neurons of the IC terminates onto inhibitory neurons of the NTS,which might represent a potential neuromodulatory target for visceral pain disorders.
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 Anhui Provincial Department of Education Outstanding Young Teachers Cultivation Key Project(No.YQZD2023046)the Anhui University of Traditional Chinese Medicine School Talent Support Program Project(Nos.DT2400000222 and DT2100000545)。
文摘Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods:The PTSD mouse model was subjected to single prolonged stress and shock(SPS&S),and the animals received 15 min sessions of EA at Shenmen acupoint(HT7).Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear.Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex(PFC).Additionally,the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.Results:Mice subjected to SPS&S presented increased anxiety-and fear-like behaviors.Lcn2 expression in the PFC was significantly upregulated following SPS&S,leading to increased expression of the proinflammatory cytokines tumor necrosis factor-a and interleukin-6 and suppression of PFC neuronal activity.However,EA at HT7 inhibited Lcn2 release,reducing neuroinflammation and hypoexcitability in the PFC.Lcn2 overexpression mitigated the effects of EA at HT7,resulting in anxiety-and fear-like behaviors.Conclusion:EA at HT7 can ameliorate PTSD-associated anxiety and fear,and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC.
基金Supported by Hunan Provincial Postgraduate Scientific Research Innovation Project(CX20231270).
文摘[Objectives]This study was conducted to investigate the alleviating effect of Phellodendri Chinensis Cortex extract on the phytotoxicity of pretilachlor in rice.[Methods]In addition to CK,Phellodendri Chinensis Cortex extract and pretilachlor with different gradients were added to the culture medium,and rice seeds with the same bud length were evenly placed in the culture medium.After 10 and 15 d of culture,the plant height and fresh weight of rice seedlings were measured and the alleviation rate was calculated.[Results]Ten days after application,the plant height of treatment 8(pretilachlor:extract concentration ratio of 25:200)was alleviated with an alleviation rate of 21.72%,and the fresh weight of treatment 9(pretilachlor:extract concentration ratio of 25:400)was alleviated with an alleviation rate of 31.04%.Fifteen days after treatment,the plant height of treatment 6(pretilachlor:extract concentration ratio of 25:50)showed a better alleviating effect,and the fresh weight of treatment 8(pretilachlor:extract concentration ratio of 25:200)exhibited a better alleviating effect,with an alleviation rate of 22.39%.Meanwhile,it was found that the extract of Phellodendri Chinensis Cortex could alleviate the increase of POD activity in rice leaves caused by pretilachlor.Meanwhile,it was found that the extract of Phellodendri Chinensis Cortex promoted the expression of CAT in rice seedlings,thus significantly increasing its activity and alleviating the toxicity of pretilachlor to rice.[Conclusions]This study can provide technical support for the screening and field application of plant-derived safeners.
文摘Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working memory,and emotional regulation,is notably impaired in this condition.This review consolidates current insights into the role of PFC dysfunction in schizophrenia,with a focus on its implications for therapeutic strategies.The neuroanatomical and neurobiological foundations of PFC dysfunction are explored,emphasizing structural abnormalities,functional dysconnectivity,and microcircuit disruptions that contribute to cognitive deficits and impaired decision-making.Clinical implications are discussed,particularly the correlation between PFC dysfunction and the severity and progression of schizophrenia symptoms.Additionally,pharmacological and non-pharmacological approaches aimed at modulating PFC activity are reviewed as potential therapeutic options.In conclusion,a deeper understanding of PFC dysfunction is pivotal for developing targeted treatments,and ongoing research offers promising avenues for enhancing outcomes for individuals affected by this debilitating disorder.
基金supported by the Major Research Instrument Development Project of the National Natural Science Foundation of China(82327810)the Foundation of the President of Hebei University(XZJJ202202)the Hebei Province“333 talent project”(A202101058).
文摘Within the prefrontal-cingulate cortex,abnormalities in coupling between neuronal networks can disturb the emotion-cognition interactions,contributing to the development of mental disorders such as depression.Despite this understanding,the neural circuit mechanisms underlying this phenomenon remain elusive.In this study,we present a biophysical computational model encompassing three crucial regions,including the dorsolateral prefrontal cortex,subgenual anterior cingulate cortex,and ventromedial prefrontal cortex.The objective is to investigate the role of coupling relationships within the prefrontal-cingulate cortex networks in balancing emotions and cognitive processes.The numerical results confirm that coupled weights play a crucial role in the balance of emotional cognitive networks.Furthermore,our model predicts the pathogenic mechanism of depression resulting from abnormalities in the subgenual cortex,and network functionality was restored through intervention in the dorsolateral prefrontal cortex.This study utilizes computational modeling techniques to provide an insight explanation for the diagnosis and treatment of depression.
基金supported by the German Research Foundation (SFB-TR 295)(to MM)。
文摘Pathological tremor is one of the cardinal symptoms in Parkinson's disease (PD).Tremor is comprised of involuntary,rhythmic,a nd oscillating movements that can vary according to the circumstances under which they occur,the body parts that are involved,and the frequency at which they present.For example,tremors can be mild to severe,are stress sensitive,and can affect arms,legs,or the head (Dirkx and Bologna,2022).
基金supported by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences,China(Grant Nos.:CI2023E002 and CI2021A04513)the National Natural Science Foundation of China(Grant Nos.:82204619 and 82274094)the Fundamental Research Funds for the Central Public Welfare Research Institutes,China(Grant Nos.:ZZ15-YQ-067 and ZZ16-ND-10-26).
文摘A strategy combining a tailored database and high-throughput activity screening that discover bioactive metabolites derived from Magnoliae Officinalis Cortex(MOC)was developed and implemented to rapidly profile and discover bioactive metabolites in vivo derived from traditional Chinese medicine(TCM).The strategy possessed four characteristics:1)The tailored database consisted of metabolites derived from big data-originated reference compound,metabolites predicted in silico,and MOC chemical profile-based pseudomolecular ions.2)When profiling MOC-derived metabolites in vivo,attentions were paid not only to prototypes of MOC compounds and metabolites directly derived from MOC compounds,as reported by most papers,but also to isomerized metabolites and the degradation products of MOC compounds as well as their derived metabolites.3)Metabolite traceability was performed,especially to distinguish isomeric prototypes-derived metabolites,prototypes of MOC compounds as well as phase I metabolites derived from other MOC compounds.4)Molecular docking was utilized for high-throughput activity screening and molecular dynamic simulation as well as zebrafish model were used for verification.Using this strategy,134 metabolites were swiftly characterized after the oral administration of MOC to rats,and several metabolites were reported for the first time.Furthermore,17 potential active metabolites were discovered by targeting the motilin,dopamine D2,and the serotonin type 4(5-HT4)receptors,and part bioactivities were verified using molecular dynamic simulation and a zebrafish constipation model.This study extends the application of mass spectrometry(MS)to rapidly profile TCM-derived metabolites in vivo,which will help pharmacologists rapidly discover potent metabolites from a complex matrix.
基金supported by grants from the National Natural Science Foundation of China(31970902,U22A20306,and 3192010300)the Municipal Administration of Hospitals Incubating Program(PZ2023009)+1 种基金the Key-Area R&D Program of Guangdong Province(2019B030335001)the Autism Research Special Fund of Zhejiang Foundation for Disabled Persons(2022003).
文摘Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivity of basolateral amygdala(BLA)pyramidal neurons(PNs)in Shank3 InsG3680 knock-in(InsG3680+/+)mice is involved in the development of anxiety.Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs.Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+mice.Further study found that the diminished control of the BLA by medial prefrontal cortex(mPFC)and optogenetic activation of the mPFC-BLA pathway also had a rescue effect,which increased the feedforward inhibition of the BLA.Taken together,our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+mice.
基金supported by the National Natural Science Foundation of China,No.82271115(to MY).
文摘Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.
基金supported by the National Natural Foundation of China(32371049,32271053,31872774,81974166,81821092,82101303,32271053,and 32000749)the Beijing Natural Science Foundation(L222016)+1 种基金the China Postdoctoral Science Foundation(2020M670061)the Tianjin Key Laboratory of Brain Science and Neuroengineering.
文摘The prelimbic cortex(PL)is actively engaged in pain modulation.The infralimbic cortex(IL)has been reported to regulate the PL.However,how this regulation affects pain remains unclear.In the present study,we recorded temporary hyper-activity of PL pyramidal neurons responding to nociceptive stimuli,but a temporary hypofunction of the IL by in vivo electrophysiological recording in rats with peripheral inflammation.Manipulation of the PL or IL had opposite effects on thermal hyperalgesia.Furthermore,the functional connectivity and chemogenetic regulation between the subregions indicated an inhibitory influence of the IL on the PL.Activation of the pathway from the IL to the PL alleviated thermal hyperalgesia,whereas its inhibition exacerbated chronic pain.Overall,our results suggest a new mechanism underlying the role of the medial prefrontal cortex in chronic pain:hypo-function of the IL leads to hyperactivity of the PL,which regulates thermal hyperalgesia,and thus contributes to the chronicity of pain.
基金supported by the National Natural Science Foundation of ChinaNos.32170950(to LY),31970915(to LY),31871170(to CL)+4 种基金the Natural Science Foundation of Guangdong Province for Major Cultivation ProjectNo.2018B030336001(to LY)the Natural Science Foundation of Guangdong Province,Nos.2021A1515010804(to CL),2023A1515010899(to CL)the Guangdong Grant‘Key Technologies for Treatment of Brain Disorders’No.2018B030332001(to CL)。
文摘Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.
