scholarly journals Mild stress accumulation limits GABAergic synaptic plasticity in the lateral habenula

2021 ◽  
Author(s):  
Arnaud L. Lalive ◽  
Alvaro Nuno‐Perez ◽  
Anna Tchenio ◽  
Manuel Mameli
Keyword(s):  
Synaptic Plasticity ◽  
Mild Stress ◽  
Lateral Habenula ◽  
Stress Accumulation

scholarly journals Chronic Unexpected Mild Stress Destroys Synaptic Plasticity of Neurons through a Glutamate Transporter, GLT-1, of Astrocytes in the Ischemic Stroke Rat

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Dafan Yu ◽  
Zhenxing Cheng ◽  
Abdoulaye Idriss Ali ◽  
Jiamin Wang ◽  
Kai Le ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Average Distance ◽  
Glutamate Transporter ◽  
Synaptic Cleft ◽  
Mild Stress ◽  
Poststroke Depression ◽  
Transmission Electron ◽  
Synaptic Formation

Background and Objective. Chronic unexpected mild stress (CUMS) destroys synaptic plasticity of hippocampal regenerated neurons that may be involved in the occurrence of poststroke depression. Astrocytes uptake glutamate at the synapse and provide metabolic support for neighboring neurons. Currently, we aim to investigate whether CUMS inhibits synaptic formation of regenerated neurons through a glutamate transporter, GLT-1, of astrocytes in the ischemic stroke rats. Method. We exposed the ischemic stroke rats to ceftriaxone, during the CUMS intervention period to determine the effects of GLT-1 on glutamate circulation by immunofluorescence and mass spectrometry and its influences to synaptic plasticity by western blot and transmission electron microscopy. Result. CUMS evidently reduced the level of astroglial GLT-1 in the hippocampus of the ischemic rats (p<0.05), resulting in smaller amount of glutamate being transported into astrocytes surrounding synapses (p<0.05), and then expression of synaptophysin was suppressed (p<0.05) in hippocampal dentate gyrus. The ultrastructures of synapses in dentate gyrus were adversely influenced including decreased proportion of smile synapses, shortened thickness of postsynaptic density, reduced number of vesicles, and widened average distance of the synaptic cleft (all p<0.05). Moreover, ceftriaxone can promote glutamate circulation and synaptic plasticity (all p<0.05) by raising astroglial GLT-1 (p<0.05) and then improve depressive behaviors of the CUMS-induced model rats (p<0.05). Conclusion. Our study shows that CUMS destroys synaptic plasticity of regenerated neurons in the hippocampus through a glutamate transporter, GLT-1, of astrocytes in the ischemic stroke rats. This may indicate one potential pathogenesis of poststroke depression.

scholarly journals S-Ketamine Exerts Antidepressant Effects by Regulating Rac1 Gtpase Mediated Synaptic Plasticity in the Hippocampus of Stressed Rats

2021 ◽  
Author(s):  
Xianlin Zhu ◽  
Fan Zhang ◽  
Yufeng You ◽  
Hongbai Wang ◽  
Su Yuan ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Molecular Mechanisms ◽  
Electrophysiological Study ◽  
Transmission Function ◽  
Long Term Potentiation ◽  
Neuronal Morphology ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Antidepressant Effects ◽  
Expression And Activity

Abstract Clinical studies have found that ketamine has a rapid and lasting antidepressant effect, especially in the case of patients with major depressive disorder (MDD). The molecular mechanisms, however, remain unclear. In this study, we observe the effects of S-Ketamine on the expression of Rac1, neuronal morphology, and synaptic transmission function in the hippocampus of stressed rats. Chronic unpredictable mild stress (CUMS) was used to construct stressed rats. The rats were given a different regimen of ketamine (20mg/kg, i.p.) and Rac1 inhibitor NSC23766 (50µg, ICV) treatment. The depression-like behavior of rats was evaluated by sucrose preference test and open-field test. The protein expression of Rac1, Glur1, synapsin1, and PSD95 in the hippocampus was detected by Western blot. Pull-down analysis was used to examine the activity of Rac1. Golgi staining and electrophysiological study were used to observe the neuronal morphology and long-term potentiation (LTP). Our results showed that ketamine can up-regulate the expression and activity of Rac1; increase the spine density and the expression of synaptic-related proteins such as Glur1, Synapsin1, and PSD95 in the hippocampus of stressed rats; reduce the CUMS-induced LTP impairments; and consequently improve depression-like behavior. However, Rac1 inhibitor NSC23766 could have effectively reversed ketamine-mediated changes in the hippocampus of rats and counteracted its antidepressant effects. The specific mechanism of S-ketamine's antidepressant effect may be related to the up-regulation of the expression and activity of Rac1 in the hippocampus of stressed rats, thus enhancing synaptic plasticity.

scholarly journals Ketamine Induces Lasting Antidepressant Effects by Modulating the NMDAR/CaMKII-Mediated Synaptic Plasticity of the Hippocampal Dentate Gyrus in Depressive Stroke Model

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Idriss Ali Abdoulaye ◽  
Shan-shan Wu ◽  
Enkhmurun Chibaatar ◽  
Da-fan Yu ◽  
Kai Le ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Brain Regions ◽  
Artery Occlusion ◽  
Mild Stress ◽  
Sprague Dawley ◽  
Poststroke Depression ◽  
Hippocampal Dentate Gyrus ◽  
Downstream Signaling ◽  
Antidepressant Effects

Background. Ketamine has been shown to possess lasting antidepressant properties. However, studies of the mechanisms involved in its effects on poststroke depression are nonexistent. Methods. To investigate these mechanisms, Sprague-Dawley rats were treated with a single local dose of ketamine after middle cerebral artery occlusion and chronic unpredicted mild stress. The effects on the hippocampal dentate gyrus were analyzed through assessment of the N-methyl-D-aspartate receptor/calcium/calmodulin-dependent protein kinase II (NMDAR/CaMKII) pathway, synaptic plasticity, and behavioral tests. Results. Ketamine administration rapidly exerted significant and lasting improvements of depressive symptoms. The biochemical analysis showed rapid, selective upregulation and downregulation of the NMDAR2-β and NMDAR2-α subtypes as well as their downstream signaling proteins β-CaMKII and α-phosphorylation in the dentate gyrus, respectively. Furthermore, the colocalization analysis indicated a significant and selectively increased conjunction of β-CaMKII and postsynaptic density protein 95 (PSD95) coupled with a notable decrease in NMDAR2-β association with PSD95 after ketamine treatment. These changes translated into significant and extended synaptic plasticity in the dentate gyrus. Conclusions. These findings not only suggest that ketamine represents a viable candidate for the treatment of poststroke depression but also that ketamine’s lasting antidepressant effects might be achieved through modulation of NMDAR/CaMKII-induced synaptic plasticity in key brain regions.

scholarly journals Electroacupuncture improves synaptic plasticity by regulating the 5-HT1A receptor in hippocampus of rats with chronic unpredictable mild stress

2020 ◽  
Vol 48 (5) ◽  
pp. 030006052091841
Author(s):  
Lixing Chen ◽  
Zengyu Yao ◽  
Shanshan Qu ◽  
Jialing Zhang ◽  
Jiping Zhang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Mrna Expression ◽  
Hippocampal Neurons ◽  
Quantitative Polymerase Chain Reaction ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Expression Levels ◽  
Mrna Expression Levels

Objectives To investigate the antidepressant effects of electroacupuncture (EA) on chronic unpredictable mild stress (CUMS) in rats, as well as the effects of EA on hippocampal neurons, synaptic morphology, and 5-hydroxytryptamine (HT) receptor expression. Methods Forty adult male Wistar rats were randomly divided into normal control, CUMS, EA, and paroxetine groups. CUMS modeling was performed for 21 days, followed by 14 days of intervention: rats in the EA group underwent stimulation of GV20 and GV29 acupuncture points for 30 minutes daily; rats in the paroxetine group were administered paroxetine daily. Behavioral tests, transmission electron microscopy, western blotting, and real-time quantitative polymerase chain reaction were used to evaluate the effects of the intervention. Results EA treatment reversed the behavioral changes observed in rats due to CUMS modeling; it also improved the pathological changes in organelles and synaptic structures of hippocampal neurons, and upregulated the protein and mRNA expression levels of 5-HT1A receptor. There were no significant differences in 5-HT1B receptor protein and mRNA expression levels among the groups. Conclusions EA treatment can alleviate depression-like symptoms in CUMS rats. The underlying mechanism may include promoting the expression of 5-HT1A receptor mRNA and protein, thereby improving synaptic plasticity in the hippocampus.

scholarly journals Electroacupuncture Reverses CUMS-Induced Depression-Like Behaviors and LTP Impairment in Hippocampus by Downregulating NR2B and CaMK II Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Shuo Jiang ◽  
Zui Shen ◽  
Wenlin Xu
Keyword(s):  
Synaptic Plasticity ◽  
Global Mental Health ◽  
Hippocampal Slices ◽  
Preference Test ◽  
Long Term Potentiation ◽  
Antidepressant Effect ◽  
Feeding Time ◽  
Mild Stress ◽  
Protein Levels ◽  
Behavior Of Rats

Objective. Depression is a global mental health problem with high disability rate, which brings a huge disease burden to the world. Electroacupuncture (EA) has been shown to be an effective method for the treatment of depression. However, the mechanism underling the antidepressant effect of EA has not been clearly clarified. The change of synaptic plasticity is the focus in the study of antidepressant mechanism. This study will observe the effect of EA on LTP of hippocampal synaptic plasticity and explore its possible mechanism. Methods. The depression-like behavior rat model was established by chronic unpredictable mild stress (CUMS). EA stimulation (Hegu and Taichong) was used to treat the depressed rats. The depression-like behavior of rats was tested by weight measurement, open field test, depression preference test, and novelty suppressed feeding test. Long-term potentiation (LTP) was recorded at CA1 synapses in hippocampal slices by electrophysiological method. N-methyl-D-aspartate receptor subunit 2B (NR2B) and calmodulin-dependent protein kinase II (CaMK II) protein levels were examined by using western blot. Results. After the establishment of CUMS-induced depression model, the weight gain rate, sucrose preference rate, line crossing number, and rearing times of rats decreased, and feeding time increased. At the same time, the LTP in hippocampus was impaired, and the expressions of NR2B and CaMK II were upregulated. After EA treatment, the depression-like behavior of rats was improved, the impairment of LTP was reversed, and the expression levels of NR2B and CaMK II protein were downregulated. Conclusion. EA can ameliorate depression-like behaviors by restoring LTP induction, downregulating NR2B and CaMK II expression in CUMS model rats, which might be part of the mechanism of EA antidepressant.

Asperosaponin VI Ameliorates The CMS-Induced Depressive-Like Behaviors By Inducing A Neuroprotective Microglial Phenotype To Restore Hippocampal Synaptic Plasticity Via PPAR-γ Pathway

2021 ◽  
Author(s):  
Xue Jiang ◽  
Saini Yi ◽  
Qin Liu ◽  
Dapeng Su ◽  
Liangyuan Li ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Natural Compound ◽  
Chronic Mild Stress ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Synaptic Function ◽  
Mild Stress ◽  
Real Time Quantitative Pcr ◽  
Ppar Γ ◽  
Microglial Phenotype

Abstract Background: The natural compound asperosaponin VI has shown potential as an antidepressant, but how it works is unclear. Here we explored its effects on mice exposed to chronic mild stress (CMS) and the underlying molecular pathways.Methods: Mice were exposed to CMS for three weeks followed by asperosaponin VI (40 mg/kg) or imipramine (20 mg/kg) for another three weeks. Depression-like behaviors were assessed in the forced swimming test, sucrose preference test, tail suspension test, open field test and novelty-suppressed feeding test. Microglial phenotype and synaptic plasticity were evaluated using immunofluorescence staining, real-time quantitative PCR and enzyme-linked immunosorbent assays in hippocampus of mice. In some experiments, stressed animals were treated with the PPAR-γ antagonist GW9622 to examine its involvement in the effects of asperosaponin VI.Results: Asperosaponin VI ameliorated depression-like behaviors of CMS mice based on all three behavioral tests, and this was associated with a switch of hippocampal microglia from a pro-inflammatory (iNOS+-Iba1+) to neuroprotective (Arg-1+-Iba1+) phenotype. The natural compound also promoted interactions between hippocampal microglia and neurons by enhancing CX3CL1/CX3CR1 and CD200/CD200R, and preserved synaptic plasticity based on PSD95 and CamKIIa levels. These effects of asperosaponin VI were blocked by GW9662. Conclusion: CMS in mice induces a proinflammatory microglial phenotype, disrupting neuron-microglia communication and synaptic function in hippocampus, ultimately leading to depression-like behaviors. Asperosaponin VI may ameliorate the effects of CMS by inducing microglia to adopt a PPAR-γ-dependent neuroprotective phenotype.

scholarly journals Electroacupuncture Ameliorates Depression-Like Behaviour in Rats by Enhancing Synaptic Plasticity via the GluN2B/CaMKII/CREB Signalling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Kun Zhang ◽  
Ran Liu ◽  
Jingruo Zhang ◽  
Xifang Wei ◽  
Yuan Gao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Preference Test ◽  
Pathological Process ◽  
Signalling Pathway ◽  
Mild Stress ◽  
Nissl Staining ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Immobility Time ◽  
Sucrose Preference Test

Background. Hippocampal synaptic plasticity during the pathological process of depression has received increasing attention. Hippocampal neuron atrophy and the reduction in synaptic density induced by chronic stress are important pathological mechanisms of depression. Electroacupuncture (EA) exerts beneficial effects on depression, but the mechanism is unclear. This study explored the effect of EA on synaptic plasticity and the potential mechanism. Methods. Forty-eight SD rats were randomly divided into the control, chronic unpredictable mild stress (CUMS), EA, and fluoxetine (FLX) groups, and each group consisted of 12 rats. The sucrose preference test, open field test, and forced swimming test were used for the evaluation of depression-like behaviour, and Golgi and Nissl staining were used for the assessment of synaptic plasticity. Western blotting and immunofluorescence were conducted to detect proteins related to synaptic plasticity and to determine their effects on signalling pathways. Results. We found that CUMS led to depression-like behaviours, including a reduced preference for sucrose, a prolonged immobility time, and reduced exploration activity. The dendritic spine densities and neuron numbers and the protein levels of MAP-2, PSD-95, and SYN were decreased in the hippocampi of rats with CUMS-induced depression, and these trends were reversed by EA. The molecular mechanism regulating this plasticity may involve the GluN2B/CaMKII/CREB signalling pathway. Conclusion. These results suggest that EA can improve depression-like behaviour and hippocampal plasticity induced by CUMS, and the mechanism may be related to the GluN2B/CaMKII/CREB pathway.

scholarly journals Effects of Chronic Stress on Cognition in Male SAMP8 Mice

2016 ◽  
Vol 39 (3) ◽  
pp. 1078-1086 ◽  
Author(s):  
Jinhua Wang ◽  
Jie Yuan ◽  
Jingjuan Pang ◽  
Jiang Ma ◽  
Bing Han ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Chronic Stress ◽  
Morris Water Maze ◽  
Water Maze ◽  
Cognitive Deficit ◽  
Brain Aging ◽  
Mild Stress ◽  
Samp8 Mice ◽  
The Impact ◽  
Senescence Accelerated Mouse

Background/Aims: Chronic stress can lead to cognitive impairment. Senescence-accelerated mouse prone 8 (SAMP8) is a naturally occurring animal model that is useful for investigating the neurological mechanisms of Alzheimer's disease. Here we investigated the impact and mechanisms of chronic stress on cognition in male SAMP8 mice. Methods: Male 6-month- old SAMP8 and SAMR1 (senescence-accelerated mouse resistant 1) mice strains were randomly divided into 4 groups. Mice in the unpredictable chronic mild stress (UCMS) groups were exposed to diverse stressors for 4 weeks. Then, these mice performed Morris water maze (MWM) test to assess the effect of UCMS on learning and memory. To explore the neurological mechanisms of UCMS on cognition in mice, we evaluated changes in the expression of postsynaptic density 95 (PSD95) and synaptophysin (SYN), which are essential proteins for synaptic plasticity. Five mice from each group were randomly chosen for reverse transcription polymerase chain reaction (RT-PCR) and western blotting analysis of SYN and PSD95. Results: The Morris water maze experiment revealed that the cognitive ability of the SAMP8 mice decreased with brain aging, and that chronic stress aggravated this cognitive deficit. In addition, chronic stress decreased the mRNA and protein expression of SYN and PSD95 in the hippocampus of the SAMP8 mice; however, the SAMR1 mice were unaffected. Conclusion: Our results demonstrate that decreased cognition and synaptic plasticity are related to aging. Moreover, we show that chronic stress aggravated this cognitive deficit and decreased SYN and PSD95 expression in the SAMP8 mice. Furthermore, the SAMP8 mice were more vulnerable to the detrimental effects of chronic stress on cognition than the SAMR1 mice. Our results suggest that the neurological mechanisms of chronic stress on cognition might be associated with a decrease in hippocampal SYN and PSD95 expression, which is critical for structural synaptic plasticity.

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