The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain functio...The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.展开更多
Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types...Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.展开更多
Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-...Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.展开更多
The central amygdala(CeA)is a crucial modulator of emotional,behavioral,and autonomic functions,including cardiovascular responses.Despite its importance,the specific circuit by which the CeA modulates blood pressure ...The central amygdala(CeA)is a crucial modulator of emotional,behavioral,and autonomic functions,including cardiovascular responses.Despite its importance,the specific circuit by which the CeA modulates blood pressure remains insufficiently explored.Our investigations demonstrate that photostimulation of GABAergic neurons in the centromedial amygdala(CeMGABA),as opposed to those in the centrolateral amygdala(CeL),produces a depressor response in both anesthetized and freely-moving mice.In addition,activation of CeMGABA axonal terminals projecting to the nucleus tractus solitarius(NTS)significantly reduces blood pressure.These CeMGABA neurons form synaptic connections with NTS neurons,allowing for the modulation of cardiovascular responses by influencing the caudal or rostral ventrolateral medulla.Furthermore,CeMGABA neurons targeting the NTS receive dense inputs from the CeL.Consequently,stimulation of CeMGABA neurons elicits hypotension through the CeM-NTS circuit,offering deeper insights into the cardiovascular responses associated with emotions and behaviors.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
Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to stressors.In the present study,the effect of chronic unpredictable mild stress（CUMS）on ...Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to stressors.In the present study,the effect of chronic unpredictable mild stress（CUMS）on CRH neurons was investigated in rat brain.Methods The rats were exposed to one of the stressors each day for 21 d.Immunostaining was performed to detect the CRH-positive neurons in the paraventricular nucleus（PVN）of the hypothalamus and in amygdala.Results After the stress protocol,the animals showed a reduction in body weight gain as well as reduced sucrose preference and locomotor activity.Interestingly,the CRH neurons in both PVN and central nucleus of the amygdala（CeA）were stimulated by CUMS.The densities of CRH-containing neurons in both PVN and CeA were significantly higher than those in control group.Conclusion The CRH systems in PVN and CeA may both contribute to depression-like behaviors during CUMS.展开更多
The amygdala,which is involved in various behaviors and emotions,is reported to connect with the whole brain.However,the long-range inputs of distinct cell types have not yet been defined.Here,we used a retrograde tra...The amygdala,which is involved in various behaviors and emotions,is reported to connect with the whole brain.However,the long-range inputs of distinct cell types have not yet been defined.Here,we used a retrograde trans-synaptic rabies virus to generate a whole-brain map of inputs to the main cell types in the mouse amygdala.We identified 37 individual regions that projected to neurons expressing vesicular glutamate transporter 2,78 regions to parvalbumin-expressing neurons,104 regions to neurons expressing protein kinase C-δ,and 89 regions to somatostatin-expressing neurons.The amygdala received massive projections from the isocortex and striatum.Several nuclei,such as the caudate-putamen and the CA1 field of the hippocampus,exhibited input preferences to different cell types in the amygdala.Notably,we identified several novel input areas,including the substantia innominata and zona incerta.These findings provide anatomical evidence to help understand the precise connections and diverse functions of the amygdala.展开更多
The short allele of the serotonin-transporter gene is associated with higher risk for anxiety and depression in Caucasians, but this association is still unclear in Asians. Here, we addressed this issue using behavior...The short allele of the serotonin-transporter gene is associated with higher risk for anxiety and depression in Caucasians, but this association is still unclear in Asians. Here, we addressed this issue using behavioral and multi-modal MRI approaches in a large group of healthy Han Chinese participants （n = 233）. In contrast to findings in Caucasians, we found that long-allele （L） carriers had higher anxiety scores. In another group （n = 64） experiencing significant levels of depression or anxiety, the L-allele frequency was also significantly higher. In healthy participants, L-carriers had reduced functional and anatomical connectivity between the amygdala and prefrontal cortex （PFC）, which was correlated with anxiety or depression scores. Our findings demonstrated that in Chinese Han participants, in contrast to Caucasians, the L-allele confers vulnerability to anxiety or depression and weakens top-down emotional control between the PFC and amygdala. Therefore, ethnic background should be taken into account in gene-related studies and their potential clinical applications.展开更多
Restraint water-immersion stress(RWIS), a compound stress model, has been widely used to induce acute gastric ulceration in rats. A wealth of evidence suggests that the central nucleus of the amygdala(CEA) is a focal ...Restraint water-immersion stress(RWIS), a compound stress model, has been widely used to induce acute gastric ulceration in rats. A wealth of evidence suggests that the central nucleus of the amygdala(CEA) is a focal region for mediating the biological response to stress. Different stressors induce distinct alterations of neuronal activity in the CEA; however, few studies have reported the characteristics of CEA neuronal activity induced by RWIS. Therefore, we explored this issue using immunohistochemistry and in vivo extracellular single-unit recording. Our results showed that RWIS and restraint stress(RS) differentially changed the c-Fos expression and firing properties of neurons in the medial CEA. In addition,RWIS, but not RS, induced the activation of corticotropinreleasing hormone neurons in the CEA. These findings suggested that specific neuronal activation in the CEA is involved in the formation of RWIS-induced gastric ulcers.This study also provides a possible theoretical explanation for the different gastric dysfunctions induced by different stressors.展开更多
Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is st...Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 （ET-1） into the dorsal hippo- campus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also elimi- nated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1- induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.展开更多
Chronic stress leads to many psychiatric disorders,including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala(BLA).However,not all individuals develop psychi...Chronic stress leads to many psychiatric disorders,including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala(BLA).However,not all individuals develop psychiatric diseases,many showing considerable resilience against stress exposure.Whether BLA neuronal activity is involved in regulating an individual’s vulnerability to stress remains elusive.In this study,using a mouse model of chronic social defeat stress(CSDS),we divided the mice into susceptible and resilient subgroups based on their social interaction behavior.Using in vivo fiber photometry and in vitro patch-clamp recording,we showed that CSDS persistently(after 20 days of recovery from stress)increased BLA neuronal activity in all the mice regardless of their susceptible or resilient nature,although impaired social interaction behavior was only observed in susceptible mice.Increased anxiety-like behavior,on the other hand,was evident in both groups.Notably,the CSDS-induced increase of BLA neuronal activity correlated well with the heightened anxiety-like but not the social avoidance behavior in mice.These findings provide new insight to our understanding of the role of neuronal activity in the amygdala in mediating stress-related psychiatric disorders.展开更多
Rapid detection and response to visual threats are critical for survival in animals.The amygdala(AMY)is hypothesized to be involved in this process,but how it interacts with the visual system to do this remains unclea...Rapid detection and response to visual threats are critical for survival in animals.The amygdala(AMY)is hypothesized to be involved in this process,but how it interacts with the visual system to do this remains unclear.By recording flash-evoked potentials simultaneously from the superior colliculus(SC),lateral posterior nucleus of the thalamus,AMY,lateral geniculate nucleus(LGN)and visual cortex,which belong to the cortical and subcortical pathways for visual fear processing,we investigated the temporal relationship between these regions in visual processing in rats.A quick flash-evoked potential(FEP)component was identified in the AMY.This emerged as early as in the LGN and was approximately 25 ms prior to the earliest component recorded in the SC,which was assumed to be an important area in visual fear.This quick P1 component in the AMY was not affected by restraint stress or corticosterone injection,but was diminished by RU38486,a glucocorticoid receptor blocker.By injecting a monosynaptic retrograde AAV tracer into the AMY,we found that it received a direct projection from the retina.These results confirm the existence of a direct connection from the retina to the AMY,that the latency in the AMY to flashes is equivalent to that in the sensory thalamus,and that the response is modulated by glucocorticoids.展开更多
The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and anxiety.Meanwhile,the endocannabinoid system plays a crucial role in regul...The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and anxiety.Meanwhile,the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor(CB1R),which is strongly expressed in the amygdala of non-human primates(NHPs).However,it remains largely unknown how the CB1Rs in the amygdala of NHPs regulate mental diseases.Here,we investigated the role of CB1R by knocking down the cannabinoid receptor 1(CNR1)gene encoding CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA.We found that CB1R knockdown in the amygdala induced anxiety-like behaviors,including disrupted night sleep,agitated psychomotor activity in new environments,and reduced social desire.Moreover,marmosets with CB1R-knockdown had up-regulated plasma cortisol levels.These results indicate that the knockdown of CB1Rs in the amygdala induces anxiety-like behaviors in marmosets,and this may be the mechanism underlying the regulation of anxiety by CB1Rs in the amygdala of NHPs.展开更多
Objective:To investigate the distribution of the motilin receptor in the amygdala of rats and its role in regulating the duodenal migrating myoelectric complex(MMC).Methods:The distribution of motilin receptor in the ...Objective:To investigate the distribution of the motilin receptor in the amygdala of rats and its role in regulating the duodenal migrating myoelectric complex(MMC).Methods:The distribution of motilin receptor in the amygdala in adult SD rats was detected by immunohistochemistry methods,and the duodenal interdigestive MMC was recorded via the electrodes implanted in the duodenum and analyzed us- ing a multichannel recorder.Results:Motilin receptor was observed in the amygdala of rats.The great amount of motilin receptor was found in the medial amygdaloid nucleus,which was also abundant in the basolateral nucleus but less abundant in the basomedial amygdaloid nucleus,the central amygdaloid nucle- us and the lateral amygdaloid nucleus.The shortening of the duodenal MMC cycle duration and the in- crease of the amplitude and the frequency of phase $ were recorded after motilin receptors being bound with exogenous motilin in the amygdala.The effects could be completely blocked by the subdiaphragmatic vagotomy but not by the intravenous injections of atropine,phentolamine or propranolol.Anti-motilin serum could partially block these effects,and the destruction of the basolateral nucleus of the amygdala had no significant effects on the duodenal MMC.Conclusion:Motilin receptor is present in all the subnu- clei of the amygdala,with the greatest amount of motilin receptor present in the medial amygdaloid nucle- us.Microinjections of motilin in the amygdala can shorten the duodenal MMC cycle duration and increase the amplitude and the frequency of phaseⅢ.These effects might be accomplished via the amygdala-hy- pothalamus-brainstem-vagus pathway,indicating the important role of the amygdala motilin receptor in the duodenal MMC regulation.展开更多
The purpose of this study was to evaluate the effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and its roles in epileptogenesis. Electrodes were implanted into the right amygdala of ma...The purpose of this study was to evaluate the effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and its roles in epileptogenesis. Electrodes were implanted into the right amygdala of male adult Wistar rats. Kindling was accomplished by using stimulus strength of 500 μA applied daily to the amygdala until 10 consecutive stage 5 seizues were induced. Then effect of ZM241385 was studied in fully kindled rats after intracerebroventricular administration of the drug. In addition, the effect on kindling progression was evaluated through ZM241385 injection before daily stimulation. In all experiments, behavioral changes in the rats in response to ZM241385 were monitored closely. The results showed that, in fully amygdala-kindled rats, ZM241385 (0.001–0.1 nmol/L) decreased afterdischage duration (ADD), motor seizure duration (MSD), stage 5 duration (S5D) and seizure duration (SD), but only the effect on ADD was dose-dependent. The doses of 0.001–0.1 nmol/L had no influence on stage 4 latency (S4L) and seizure stage (SS). The dosages of 0.0001 and 1 nmol/L of ZM241385 did not exert any effect on all seizure parameters. In contrast to the results in fully amygdala-kindled rats, ZM241385 (0.001–0.1 nmol/L) had minimal or no effects on the progression of amygdala-kindled seizures. We are led to the conclusion that although ZM241385 had no influence on the progression of amygdala-kindled seizures, it had potent anticonvulsant profile and little adverse effects at the dosage of 0.001–0.1 nmol/L, suggesting that the agent is effective against the amygdala-kindled seizures.展开更多
BACKGROUND The main clinical manifestation of Alzheimer’s disease(AD)is memory loss,which can be accompanied by neuropsychiatric symptoms at different stages of the disease.Amygdala is closely related to emotion and ...BACKGROUND The main clinical manifestation of Alzheimer’s disease(AD)is memory loss,which can be accompanied by neuropsychiatric symptoms at different stages of the disease.Amygdala is closely related to emotion and memory.AIM To evaluate the diagnostic value of amygdala on structural magnetic resonance imaging(sMRI)for AD.METHODS In this study,22 patients with AD and 26 controls were enrolled.Their amygdala volumes were measured by sMRI and analyzed using an automatic analysis software.RESULTS The bilateral amygdala volumes of AD patients were significantly lower than those of the controls and were positively correlated with the hippocampal volumes.Receiver operating characteristic curve analyses showed that the sensitivity of the left and right amygdala volumes in diagnosing AD was 80.8%and 88.5%,respectively.Subgroup analyses showed that amygdala atrophy was more serious in AD patients with neuropsychiatric symptoms,which mainly included irritability(22.73%),sleep difficulties(22.73%),apathy(18.18%),and hallucination(13.64%).CONCLUSION Amygdala volumes measured by sMRI can be used to diagnose AD,and amygdala atrophy is more serious in patients with neuropsychiatric symptoms.展开更多
OBJECTIVE:To investigated the effects of suspended moxibustion stimulating Shenshu(BL23)and Guanyuan(CV4)acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxi...OBJECTIVE:To investigated the effects of suspended moxibustion stimulating Shenshu(BL23)and Guanyuan(CV4)acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney-Yang deficiency symptom pattern(KYDS).METHODS:Sixty male Sprague Dawley rats were randomly divided into a control group(n=12)and an experimental group(n=48).Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model.The 48 rats successfully modeled were then randomly divided into a model group(model,n=12),a carbenoxolone intraperitoneal injection group(CBX,n=12),a moxibustion group(moxi,n=12),and a moxi+CBX group(n=12).In the moxi,the Shenshu(BL23)and Guanyuan(CV 4)acupoints were treated with moxibustion for 14 d.After treatment,measures were taken of serum levels of corticosterone(CORT),adrenocorticotropic hormone(ACTH),and corticotropinreleasing hormone(CRH).The expression of mineralocorticoid receptors(MRs),glucocorticoid receptors(GRs),11beta-hydroxysteroid dehydrogenase type 1(11β-HSD1),CRH,and ACTH in the rats’amygdala,hypothalamus,or pituitary(as appropriate)was detected.Data were analyzed using one-way analysis of variance.RESULTS:Compared with those of the control group,the serum levels of CRH,ACTH,and CORT;the mRNA and protein expressions of MR,GR,and 11β-HSD1 in the amygdala;the mRNA and protein expressions of 11β-HSD1 in the hypothalamus;the CRH mRNA expression in the amygdala and hypothalamus;and the ACTH mRNA expression in the pituitary of the rats in the model group were all significantly decreased(P<0.05 or 0.01).After treatment with moxibustion,all the aforementioned observation indices except for 11β-HSD1 m RNA expression were ameliorated compared with those in the model group(P<0.05 or 0.01).CONCLUSIONS:Suspended moxibustion can effectively improve the serum levels of ACTH,CRH,and CORT and can up-regulate the mRNA and protein expressions of MR,GR,11β-HSD1,CRH,and ACTH in the amygdala and hypothalamus of KYDS rats.This may be one of the molecular mechanisms with which moxibustion alleviates KYDS.展开更多
AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main metabolites and amino acid neurotr...AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main metabolites and amino acid neurotransmitters concentrations were quantified using high performance liquid chromatography(HPLC). Four groups of rats were employed: saline-treated and rats receiving 250, 500 and 800 mg/kg of ayahuasca infusion(gavage). Animals were killed 40 min after drug ingestion and the structures stored at-80 ℃ until HPLC assay. The data from all groups were compared using Analysis of variance and Scheffé as post test and P < 0.05 was accepted as significant. RESULTS: The results showed decreased concentrations of glycine(GLY)(0.13 ± 0.03 vs 0.29 ± 0.07, P < 0.001) and γ-aminobutyric acid(GABA)(1.07 ± 0.14 vs 1.73 ± 0.25, P < 0.001) in the amygdala of rats that received 500 of ayahuasca. Animals that ingested 800 mg/kg of ayahuasca also showed a reduction of GLY level(0.11 ± 0.01 vs 0.29 ± 0.07, P < 0.001) and GABA(0.98 ± 0.06 vs 1.73 ± 0.25, P < 0.001). In the hippocampus, increased GABA levels were found in rats that received all ayahuasca doses: 250 mg/kg(1.29 ± 0.19 vs 0.84 ± 0.21, P < 0.05); 500 mg/kg(2.23 ± 038 vs 084 ± 0.21, P < 0.05) and 800 mg/kg(1.98 ± 0.92 vs 0.84 ± 0.21, P < 0.05). In addition, an increased utilization rate of all monoamines was found in the amygdala after ayahuasca administration in doses: 250 mg/kg(noradrenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P < 0.01; dopamine: 0.39 ± 0.012 vs 2.39 ± 0.84, P < 0.001; serotonin: 1.02 ± 0.22 vs 4.04 ± 0.91, P < 0.001), 500 mg/kg(noradrenaline: 0.08 ± 0.02 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.33 ± 0.19 vs 2.39 ± 0.84, P < 0.001; serotonin: 0.59 ± 0.08 vs 4.04 ± 0.91, P < 0.001) and 800 mg/kg(noradrenaline: 0.16 ± 0.04 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.84 ± 0.65 vs2.39 ± 0.84, P < 0.05; serotonin: 0.36 ± 0.02 vs 4.04 ± 0.91, P < 0.001). CONCLUSION: Our data suggest increased release of inhibitory amino acids by the hippocampus and an increased utilization rate of monoamines by the amygdala after different doses of ayahuasca ingestion.展开更多
Recurrent epileptic seizures can lead to brain edema, indicating that water regulation may be perturbed by seizures. We hypothesized that the expression of the brain water channel aquaporin-4 （AQP-4） may be upregula...Recurrent epileptic seizures can lead to brain edema, indicating that water regulation may be perturbed by seizures. We hypothesized that the expression of the brain water channel aquaporin-4 （AQP-4） may be upregulated in the epileptic brain. In the present study, we established the amygdala kindling model of epilepsy, and quantified AQP-4 protein and mRNA levels, using reverse transcription-PCR, immunohistochemistry and western blotting, in epileptic and control rats. We found that AQP-4 was overexpressed in the cerebral cortex of rats with epilepsy compared with controls. These findings show that AQP-4 is highly expressed in the brain of amygdala-kindled rats, suggesting that repeated seizures affect water homeostasis in the brain.展开更多
In this study we investigated whether GABAA receptors of the basolateral amygdala(BLA) interact with the effect of dexamethasone on the retrieval stage of memory.Adult male Wistar rats were bilaterally cannulated in t...In this study we investigated whether GABAA receptors of the basolateral amygdala(BLA) interact with the effect of dexamethasone on the retrieval stage of memory.Adult male Wistar rats were bilaterally cannulated in the BLA by stereotaxic surgery.The animals were trained in step-through apparatus by induction of electric shock(1.5 mA,3 s) and were tested for memory retrieval after 1 d.The time of latency for entering the dark compartment of the instrument and the time spent by rats in this chamber were recorded for evaluation of the animals' retrieval in passive avoidance memory.Administration of dexamethasone(0.3 and 0.9 mg/kg,subcutaneously(s.c.)),immediately after training,enhanced memory retrieval.This effect was reduced by intra-BLA microinjection of muscimol(0.125,0.250 and 0.500 μg/rat),when administered before 0.9 mg/kg of dexamethasone.Microinjection of bicuculline(0.75 μg/rat,intra-BLA) with an ineffective dose of dexamethasone(0.1 mg/kg,s.c.) increased memory retrieval.However,the same doses of muscimol and bicuculline without dexamethasone did not affect memory processes.Our data support reports that dexamethasone enhances memory retrieval.It seems that GABAA receptors of the BLA mediate the effect of dexamethasone on memory retrieval in rats.展开更多
基金supported by the National Natural Science Foundation of China,Nos.32371070 (to JT),31761163005 (to JT),32100824 (to QX)the Shenzhen Science and Technology Program,Nos.RCBS20210609104606024 (to QX),JCY20210324101813035 (to DL)+4 种基金the Guangdong Provincial Key S&T Program,No.2018B030336001 (to JT)the Key Basic Research Program of Shenzhen Science and Technology Innovation Commission,Nos.JCYJ20200109115405930 (to JT),JCYJ20220818101615033 (to DL),JCYJ20210324115811031 (to QX),JCYJ20200109150717745 (to QX)Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases,No.ZDSYS20220304163558001 (to JT)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,No.2023B1212060055 (to JT)the China Postdoctoral Science Foundation,No.2021M693298 (to QX)。
文摘The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.
基金supported by the STI 2030—Major Projects 2021ZD0204000,No.2021ZD0204003 (to XZ)the National Natural Science Foundation of China,Nos.32170973 (to XZ),32071018 (to ZH)。
文摘Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.
基金supported by the National Natural Science Foundation of China,Nos.32371065(to CL)and 32170950(to LY)the Natural Science Foundation of the Guangdong Province,No.2023A1515010899(to CL)the Science and Technology Projects in Guangzhou,Nos.2023A4J0578 and 2024A03J0180(to CW)。
文摘Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.
基金supported by grants from the National Natural Science Foundation of China(32171126,U23A20431)a Natural Science Foundation of Hebei Province for Innovative Research Grant Group Project(H2021206203).
文摘The central amygdala(CeA)is a crucial modulator of emotional,behavioral,and autonomic functions,including cardiovascular responses.Despite its importance,the specific circuit by which the CeA modulates blood pressure remains insufficiently explored.Our investigations demonstrate that photostimulation of GABAergic neurons in the centromedial amygdala(CeMGABA),as opposed to those in the centrolateral amygdala(CeL),produces a depressor response in both anesthetized and freely-moving mice.In addition,activation of CeMGABA axonal terminals projecting to the nucleus tractus solitarius(NTS)significantly reduces blood pressure.These CeMGABA neurons form synaptic connections with NTS neurons,allowing for the modulation of cardiovascular responses by influencing the caudal or rostral ventrolateral medulla.Furthermore,CeMGABA neurons targeting the NTS receive dense inputs from the CeL.Consequently,stimulation of CeMGABA neurons elicits hypotension through the CeM-NTS circuit,offering deeper insights into the cardiovascular responses associated with emotions and behaviors.
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.
文摘Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to stressors.In the present study,the effect of chronic unpredictable mild stress（CUMS）on CRH neurons was investigated in rat brain.Methods The rats were exposed to one of the stressors each day for 21 d.Immunostaining was performed to detect the CRH-positive neurons in the paraventricular nucleus（PVN）of the hypothalamus and in amygdala.Results After the stress protocol,the animals showed a reduction in body weight gain as well as reduced sucrose preference and locomotor activity.Interestingly,the CRH neurons in both PVN and central nucleus of the amygdala（CeA）were stimulated by CUMS.The densities of CRH-containing neurons in both PVN and CeA were significantly higher than those in control group.Conclusion The CRH systems in PVN and CeA may both contribute to depression-like behaviors during CUMS.
基金the Key Project of the National Natural Science Foundation of China(31430034)the National Key Research and Development Project of the Ministry of Science and Technology of China(2016YF051000)+3 种基金the Science and Technology Program of Guangdong Province,China(2018B030334001)the Key Realm R&D Program of Guangdong Province,China(2019B030335001)Funds for Creative Research Groups of China from the National Natural Science Foundation of China(81521062)the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2019PT310023)。
文摘The amygdala,which is involved in various behaviors and emotions,is reported to connect with the whole brain.However,the long-range inputs of distinct cell types have not yet been defined.Here,we used a retrograde trans-synaptic rabies virus to generate a whole-brain map of inputs to the main cell types in the mouse amygdala.We identified 37 individual regions that projected to neurons expressing vesicular glutamate transporter 2,78 regions to parvalbumin-expressing neurons,104 regions to neurons expressing protein kinase C-δ,and 89 regions to somatostatin-expressing neurons.The amygdala received massive projections from the isocortex and striatum.Several nuclei,such as the caudate-putamen and the CA1 field of the hippocampus,exhibited input preferences to different cell types in the amygdala.Notably,we identified several novel input areas,including the substantia innominata and zona incerta.These findings provide anatomical evidence to help understand the precise connections and diverse functions of the amygdala.
基金supported by the National Key Basic Research and Development Program(973)(2011CB707800)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB02030300)+1 种基金the Natural Science Foundation of China(91132301and81000582)the Beijing Nova Program(2010B06)
文摘The short allele of the serotonin-transporter gene is associated with higher risk for anxiety and depression in Caucasians, but this association is still unclear in Asians. Here, we addressed this issue using behavioral and multi-modal MRI approaches in a large group of healthy Han Chinese participants （n = 233）. In contrast to findings in Caucasians, we found that long-allele （L） carriers had higher anxiety scores. In another group （n = 64） experiencing significant levels of depression or anxiety, the L-allele frequency was also significantly higher. In healthy participants, L-carriers had reduced functional and anatomical connectivity between the amygdala and prefrontal cortex （PFC）, which was correlated with anxiety or depression scores. Our findings demonstrated that in Chinese Han participants, in contrast to Caucasians, the L-allele confers vulnerability to anxiety or depression and weakens top-down emotional control between the PFC and amygdala. Therefore, ethnic background should be taken into account in gene-related studies and their potential clinical applications.
基金supported by the National Natural Science Foundation of China (31571104 and 81501149)the Science and Technological Project of Shandong Province of China (2016GSF201058)
文摘Restraint water-immersion stress(RWIS), a compound stress model, has been widely used to induce acute gastric ulceration in rats. A wealth of evidence suggests that the central nucleus of the amygdala(CEA) is a focal region for mediating the biological response to stress. Different stressors induce distinct alterations of neuronal activity in the CEA; however, few studies have reported the characteristics of CEA neuronal activity induced by RWIS. Therefore, we explored this issue using immunohistochemistry and in vivo extracellular single-unit recording. Our results showed that RWIS and restraint stress(RS) differentially changed the c-Fos expression and firing properties of neurons in the medial CEA. In addition,RWIS, but not RS, induced the activation of corticotropinreleasing hormone neurons in the CEA. These findings suggested that specific neuronal activation in the CEA is involved in the formation of RWIS-induced gastric ulcers.This study also provides a possible theoretical explanation for the different gastric dysfunctions induced by different stressors.
基金supported by Major State Basic Research Program of China(Grant No.2013CB733801)
文摘Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 （ET-1） into the dorsal hippo- campus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also elimi- nated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1- induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.
基金supported by grants from the National Natural Science Foundation of China(31970953,81930032,and 81760505)the Natural Science Foundation of Jiangxi Province,China(20192ACB21024,20192ACB20023,20181ACG70003,and 20192BCB23008).
文摘Chronic stress leads to many psychiatric disorders,including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala(BLA).However,not all individuals develop psychiatric diseases,many showing considerable resilience against stress exposure.Whether BLA neuronal activity is involved in regulating an individual’s vulnerability to stress remains elusive.In this study,using a mouse model of chronic social defeat stress(CSDS),we divided the mice into susceptible and resilient subgroups based on their social interaction behavior.Using in vivo fiber photometry and in vitro patch-clamp recording,we showed that CSDS persistently(after 20 days of recovery from stress)increased BLA neuronal activity in all the mice regardless of their susceptible or resilient nature,although impaired social interaction behavior was only observed in susceptible mice.Increased anxiety-like behavior,on the other hand,was evident in both groups.Notably,the CSDS-induced increase of BLA neuronal activity correlated well with the heightened anxiety-like but not the social avoidance behavior in mice.These findings provide new insight to our understanding of the role of neuronal activity in the amygdala in mediating stress-related psychiatric disorders.
基金the National Key Research and Development Program of China(2018YFA0108503)the National Natural Science Foundation of China(81760251 and 81560234)the Yunnan Provincial Natural Science Foundation(2018FB118 and KKSY201626001).
文摘Rapid detection and response to visual threats are critical for survival in animals.The amygdala(AMY)is hypothesized to be involved in this process,but how it interacts with the visual system to do this remains unclear.By recording flash-evoked potentials simultaneously from the superior colliculus(SC),lateral posterior nucleus of the thalamus,AMY,lateral geniculate nucleus(LGN)and visual cortex,which belong to the cortical and subcortical pathways for visual fear processing,we investigated the temporal relationship between these regions in visual processing in rats.A quick flash-evoked potential(FEP)component was identified in the AMY.This emerged as early as in the LGN and was approximately 25 ms prior to the earliest component recorded in the SC,which was assumed to be an important area in visual fear.This quick P1 component in the AMY was not affected by restraint stress or corticosterone injection,but was diminished by RU38486,a glucocorticoid receptor blocker.By injecting a monosynaptic retrograde AAV tracer into the AMY,we found that it received a direct projection from the retina.These results confirm the existence of a direct connection from the retina to the AMY,that the latency in the AMY to flashes is equivalent to that in the sensory thalamus,and that the response is modulated by glucocorticoids.
基金supported by the Zhejiang Province Natural Science Foundation of China(LD22H090003)Key-Area Research and Development Program of Guangdong Province(2019B030335001 and 2018B030334001)+3 种基金the National Natural Science Foundation of China(31871070,82090031,32071097,31871056,and 32170991)the Key R&D Program of Zhejiang Province(2020C03009)Fundamental Research Funds for the Central Universities(2021FZZX001-37)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-057).
文摘The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and anxiety.Meanwhile,the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor(CB1R),which is strongly expressed in the amygdala of non-human primates(NHPs).However,it remains largely unknown how the CB1Rs in the amygdala of NHPs regulate mental diseases.Here,we investigated the role of CB1R by knocking down the cannabinoid receptor 1(CNR1)gene encoding CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA.We found that CB1R knockdown in the amygdala induced anxiety-like behaviors,including disrupted night sleep,agitated psychomotor activity in new environments,and reduced social desire.Moreover,marmosets with CB1R-knockdown had up-regulated plasma cortisol levels.These results indicate that the knockdown of CB1Rs in the amygdala induces anxiety-like behaviors in marmosets,and this may be the mechanism underlying the regulation of anxiety by CB1Rs in the amygdala of NHPs.
基金The Clinical Speciality Emphasis Topic Foundation of Department of Health(No.2004-56)
文摘Objective:To investigate the distribution of the motilin receptor in the amygdala of rats and its role in regulating the duodenal migrating myoelectric complex(MMC).Methods:The distribution of motilin receptor in the amygdala in adult SD rats was detected by immunohistochemistry methods,and the duodenal interdigestive MMC was recorded via the electrodes implanted in the duodenum and analyzed us- ing a multichannel recorder.Results:Motilin receptor was observed in the amygdala of rats.The great amount of motilin receptor was found in the medial amygdaloid nucleus,which was also abundant in the basolateral nucleus but less abundant in the basomedial amygdaloid nucleus,the central amygdaloid nucle- us and the lateral amygdaloid nucleus.The shortening of the duodenal MMC cycle duration and the in- crease of the amplitude and the frequency of phase $ were recorded after motilin receptors being bound with exogenous motilin in the amygdala.The effects could be completely blocked by the subdiaphragmatic vagotomy but not by the intravenous injections of atropine,phentolamine or propranolol.Anti-motilin serum could partially block these effects,and the destruction of the basolateral nucleus of the amygdala had no significant effects on the duodenal MMC.Conclusion:Motilin receptor is present in all the subnu- clei of the amygdala,with the greatest amount of motilin receptor present in the medial amygdaloid nucle- us.Microinjections of motilin in the amygdala can shorten the duodenal MMC cycle duration and increase the amplitude and the frequency of phaseⅢ.These effects might be accomplished via the amygdala-hy- pothalamus-brainstem-vagus pathway,indicating the important role of the amygdala motilin receptor in the duodenal MMC regulation.
基金supported by a grant from the National Natural Science Foundation of China(No.30770752)
文摘The purpose of this study was to evaluate the effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and its roles in epileptogenesis. Electrodes were implanted into the right amygdala of male adult Wistar rats. Kindling was accomplished by using stimulus strength of 500 μA applied daily to the amygdala until 10 consecutive stage 5 seizues were induced. Then effect of ZM241385 was studied in fully kindled rats after intracerebroventricular administration of the drug. In addition, the effect on kindling progression was evaluated through ZM241385 injection before daily stimulation. In all experiments, behavioral changes in the rats in response to ZM241385 were monitored closely. The results showed that, in fully amygdala-kindled rats, ZM241385 (0.001–0.1 nmol/L) decreased afterdischage duration (ADD), motor seizure duration (MSD), stage 5 duration (S5D) and seizure duration (SD), but only the effect on ADD was dose-dependent. The doses of 0.001–0.1 nmol/L had no influence on stage 4 latency (S4L) and seizure stage (SS). The dosages of 0.0001 and 1 nmol/L of ZM241385 did not exert any effect on all seizure parameters. In contrast to the results in fully amygdala-kindled rats, ZM241385 (0.001–0.1 nmol/L) had minimal or no effects on the progression of amygdala-kindled seizures. We are led to the conclusion that although ZM241385 had no influence on the progression of amygdala-kindled seizures, it had potent anticonvulsant profile and little adverse effects at the dosage of 0.001–0.1 nmol/L, suggesting that the agent is effective against the amygdala-kindled seizures.
基金Supported by The Young Talents Fund of the Second Hospital of Shandong University,No.2018YT16Rongxiang Regenerative Medicine Foundation of Shandong University,No.2019SDRX-09.
文摘BACKGROUND The main clinical manifestation of Alzheimer’s disease(AD)is memory loss,which can be accompanied by neuropsychiatric symptoms at different stages of the disease.Amygdala is closely related to emotion and memory.AIM To evaluate the diagnostic value of amygdala on structural magnetic resonance imaging(sMRI)for AD.METHODS In this study,22 patients with AD and 26 controls were enrolled.Their amygdala volumes were measured by sMRI and analyzed using an automatic analysis software.RESULTS The bilateral amygdala volumes of AD patients were significantly lower than those of the controls and were positively correlated with the hippocampal volumes.Receiver operating characteristic curve analyses showed that the sensitivity of the left and right amygdala volumes in diagnosing AD was 80.8%and 88.5%,respectively.Subgroup analyses showed that amygdala atrophy was more serious in AD patients with neuropsychiatric symptoms,which mainly included irritability(22.73%),sleep difficulties(22.73%),apathy(18.18%),and hallucination(13.64%).CONCLUSION Amygdala volumes measured by sMRI can be used to diagnose AD,and amygdala atrophy is more serious in patients with neuropsychiatric symptoms.
基金Supported by the National Natural Science Foundation of China:Study on the Mechanism of Suspension Moxibustion with Moxa Stick in Treating Hydrocortisone Rats with Kidney-Yang Deficiency based on Hippocampus(amygdala)-HPA Axis(No.81660817)。
文摘OBJECTIVE:To investigated the effects of suspended moxibustion stimulating Shenshu(BL23)and Guanyuan(CV4)acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney-Yang deficiency symptom pattern(KYDS).METHODS:Sixty male Sprague Dawley rats were randomly divided into a control group(n=12)and an experimental group(n=48).Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model.The 48 rats successfully modeled were then randomly divided into a model group(model,n=12),a carbenoxolone intraperitoneal injection group(CBX,n=12),a moxibustion group(moxi,n=12),and a moxi+CBX group(n=12).In the moxi,the Shenshu(BL23)and Guanyuan(CV 4)acupoints were treated with moxibustion for 14 d.After treatment,measures were taken of serum levels of corticosterone(CORT),adrenocorticotropic hormone(ACTH),and corticotropinreleasing hormone(CRH).The expression of mineralocorticoid receptors(MRs),glucocorticoid receptors(GRs),11beta-hydroxysteroid dehydrogenase type 1(11β-HSD1),CRH,and ACTH in the rats’amygdala,hypothalamus,or pituitary(as appropriate)was detected.Data were analyzed using one-way analysis of variance.RESULTS:Compared with those of the control group,the serum levels of CRH,ACTH,and CORT;the mRNA and protein expressions of MR,GR,and 11β-HSD1 in the amygdala;the mRNA and protein expressions of 11β-HSD1 in the hypothalamus;the CRH mRNA expression in the amygdala and hypothalamus;and the ACTH mRNA expression in the pituitary of the rats in the model group were all significantly decreased(P<0.05 or 0.01).After treatment with moxibustion,all the aforementioned observation indices except for 11β-HSD1 m RNA expression were ameliorated compared with those in the model group(P<0.05 or 0.01).CONCLUSIONS:Suspended moxibustion can effectively improve the serum levels of ACTH,CRH,and CORT and can up-regulate the mRNA and protein expressions of MR,GR,11β-HSD1,CRH,and ACTH in the amygdala and hypothalamus of KYDS rats.This may be one of the molecular mechanisms with which moxibustion alleviates KYDS.
基金Supported by Funda o de Amparo a Pesquisa do Estado de S o PauloCoordena o de Aperfei oamento de Pessoal de Nível Superior+1 种基金Conselho Nacional de Desenvolvimento Científico e TecnológicoInstituto Nacional de Neurociência Translacional
文摘AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main metabolites and amino acid neurotransmitters concentrations were quantified using high performance liquid chromatography(HPLC). Four groups of rats were employed: saline-treated and rats receiving 250, 500 and 800 mg/kg of ayahuasca infusion(gavage). Animals were killed 40 min after drug ingestion and the structures stored at-80 ℃ until HPLC assay. The data from all groups were compared using Analysis of variance and Scheffé as post test and P < 0.05 was accepted as significant. RESULTS: The results showed decreased concentrations of glycine(GLY)(0.13 ± 0.03 vs 0.29 ± 0.07, P < 0.001) and γ-aminobutyric acid(GABA)(1.07 ± 0.14 vs 1.73 ± 0.25, P < 0.001) in the amygdala of rats that received 500 of ayahuasca. Animals that ingested 800 mg/kg of ayahuasca also showed a reduction of GLY level(0.11 ± 0.01 vs 0.29 ± 0.07, P < 0.001) and GABA(0.98 ± 0.06 vs 1.73 ± 0.25, P < 0.001). In the hippocampus, increased GABA levels were found in rats that received all ayahuasca doses: 250 mg/kg(1.29 ± 0.19 vs 0.84 ± 0.21, P < 0.05); 500 mg/kg(2.23 ± 038 vs 084 ± 0.21, P < 0.05) and 800 mg/kg(1.98 ± 0.92 vs 0.84 ± 0.21, P < 0.05). In addition, an increased utilization rate of all monoamines was found in the amygdala after ayahuasca administration in doses: 250 mg/kg(noradrenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P < 0.01; dopamine: 0.39 ± 0.012 vs 2.39 ± 0.84, P < 0.001; serotonin: 1.02 ± 0.22 vs 4.04 ± 0.91, P < 0.001), 500 mg/kg(noradrenaline: 0.08 ± 0.02 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.33 ± 0.19 vs 2.39 ± 0.84, P < 0.001; serotonin: 0.59 ± 0.08 vs 4.04 ± 0.91, P < 0.001) and 800 mg/kg(noradrenaline: 0.16 ± 0.04 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.84 ± 0.65 vs2.39 ± 0.84, P < 0.05; serotonin: 0.36 ± 0.02 vs 4.04 ± 0.91, P < 0.001). CONCLUSION: Our data suggest increased release of inhibitory amino acids by the hippocampus and an increased utilization rate of monoamines by the amygdala after different doses of ayahuasca ingestion.
基金the Natural Science Foundation of Shanghai, No. 09ZR1405500the Research Projects of Shanghai Municipal Health Bureau, No. 2008-08
文摘Recurrent epileptic seizures can lead to brain edema, indicating that water regulation may be perturbed by seizures. We hypothesized that the expression of the brain water channel aquaporin-4 （AQP-4） may be upregulated in the epileptic brain. In the present study, we established the amygdala kindling model of epilepsy, and quantified AQP-4 protein and mRNA levels, using reverse transcription-PCR, immunohistochemistry and western blotting, in epileptic and control rats. We found that AQP-4 was overexpressed in the cerebral cortex of rats with epilepsy compared with controls. These findings show that AQP-4 is highly expressed in the brain of amygdala-kindled rats, suggesting that repeated seizures affect water homeostasis in the brain.
基金supported by the Shahid Chamran University of Ahvaz,Iran
文摘In this study we investigated whether GABAA receptors of the basolateral amygdala(BLA) interact with the effect of dexamethasone on the retrieval stage of memory.Adult male Wistar rats were bilaterally cannulated in the BLA by stereotaxic surgery.The animals were trained in step-through apparatus by induction of electric shock(1.5 mA,3 s) and were tested for memory retrieval after 1 d.The time of latency for entering the dark compartment of the instrument and the time spent by rats in this chamber were recorded for evaluation of the animals' retrieval in passive avoidance memory.Administration of dexamethasone(0.3 and 0.9 mg/kg,subcutaneously(s.c.)),immediately after training,enhanced memory retrieval.This effect was reduced by intra-BLA microinjection of muscimol(0.125,0.250 and 0.500 μg/rat),when administered before 0.9 mg/kg of dexamethasone.Microinjection of bicuculline(0.75 μg/rat,intra-BLA) with an ineffective dose of dexamethasone(0.1 mg/kg,s.c.) increased memory retrieval.However,the same doses of muscimol and bicuculline without dexamethasone did not affect memory processes.Our data support reports that dexamethasone enhances memory retrieval.It seems that GABAA receptors of the BLA mediate the effect of dexamethasone on memory retrieval in rats.
