Effects of chronic mild stress induced depression on synaptic plasticity in mouse hippocampus

2019 ◽  
Vol 365 ◽  
pp. 26-35 ◽  
Author(s):  
Maofang Hei ◽  
Peng Chen ◽  
Shuzhong Wang ◽  
Xuzhao Li ◽  
Mingrui Xu ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Mouse Hippocampus

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 Deficiency in Androgen Receptor Aggravates the Depressive-Like Behaviors in Chronic Mild Stress Model of Depression

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1021 ◽  
Author(s):  
Hung ◽  
Huang ◽  
Chang ◽  
Kang
Keyword(s):  
Androgen Receptor ◽  
Chronic Mild Stress ◽  
Mapk Signaling ◽  
Mild Stress ◽  
Therapeutic Approaches ◽  
Bdnf Expression ◽  
Bdnf Mrna ◽  
Major Depressive ◽  
Mouse Hippocampus ◽  
The Brain

While androgen receptor (AR) and stress may influence the development of the major depressive disorder (MDD), the detailed relationship, however, remains unclear. Here we found loss of AR accelerated development of depressive-like behaviors in mice under chronic mild stress (CMS). Mechanism dissection indicated that AR might function via altering the expression of miR-204-5p to modulate the brain-derived neurotrophic factor (BDNF) expression to influence the depressive-like behaviors in the mice under the CMS. Adding the antiandrogen flutamide with the stress hormone corticosterone can additively decrease BDNF mRNA in mouse hippocampus mHippoE-14 cells, which can then be reversed via down-regulating the miR-204-5p expression. Importantly, targeting this newly identified AR-mediated miR-204-5p/BDNF/AKT/MAPK signaling with small molecules including 7,8-DHF and fluoxetine, all led to alter the depressive-like behavior in AR knockout mice under CMS exposure. Together, results from these preclinical studies conclude that decreased AR may accelerate the stress-induced MDD via altering miR-204-5p/BDNF/AKT/MAPK signaling, and targeting this newly identified signaling may help in the development of better therapeutic approaches to reduce the development of MDD.

scholarly journals MicroRNA-99a is a Potential Target for Regulating Hypothalamic Synaptic Plasticity in the Peri/Postmenopausal Depression Model

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1081 ◽  
Author(s):  
Jin Yang ◽  
Ling Zhang ◽  
Lu-Lu Cao ◽  
Jun Qi ◽  
Ping Li ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nuclear Translocation ◽  
Chronic Mild Stress ◽  
Synaptic Proteins ◽  
Mild Stress ◽  
Fk506 Binding Protein ◽  
Electrophysiological Recordings ◽  
Menopausal Women ◽  
Serum Hormone ◽  
Postmenopausal Depression

Accumulating evidence has demonstrated that there is a growing trend of menopausal women suffering from depression. However, the pathogenesis of menopausal depression still remains unclear. Hence, this paper aims to reveal the pathological mechanisms involved in postmenopausal depression by using a novel peri- to postmenopausal depression model induced by a two-step ovariectomy plus chronic mild stress (CMS). The results of metabolic chambers and serum hormone/cytokine determination revealed that peri/postmenopausal depressive mice exhibited endocrine and metabolic disorders. Electrophysiological recordings indicated that the hippocampal synaptic transmission was compromised. Compared to the sham group, the microRNA-99a (miR-99a) level decreased significantly in the hypothalamus, and its target FK506-binding protein 51 (FKBP51) enormously increased; in contrast, the nuclear translocation of the progesterone receptor (PR) decreased in hypothalamic paraventricular nucleus (PVN) in the peri/postmenopausal depression mouse model. Additionally, synaptic proteins, including postsynaptic density protein 95 (PSD-95) and synaptophysin (SYN), showed a similar decrease in the hypothalamus. Accordingly, the present work suggests that miR-99a may be involved in the regulation of hypothalamic synaptic plasticity and that it might be a potential therapeutic target for peri/postmenopausal depression.

scholarly journals Chronic mild stress alters synaptic plasticity in the nucleus accumbens through GSK3β-dependent modulation of Kv4.2 channels

2020 ◽  
Vol 117 (14) ◽  
pp. 8143-8153 ◽  
Author(s):  
Giuseppe Aceto ◽  
Claudia Colussi ◽  
Lucia Leone ◽  
Salvatore Fusco ◽  
Marco Rinaudo ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nucleus Accumbens ◽  
Viral Vector ◽  
Glycogen Synthase ◽  
Chronic Mild Stress ◽  
Long Term Potentiation ◽  
Spike Timing ◽  
Mild Stress

Although major depressive disorder (MDD) is highly prevalent, its pathophysiology is poorly understood. Recent evidence suggests that glycogen-synthase kinase 3β (GSK3β) plays a key role in memory formation, yet its role in mood regulation remains controversial. Here, we investigated whether GSK3β activity in the nucleus accumbens (NAc) is associated with depression-like behaviors and synaptic plasticity. We performed whole-cell patch-clamp recordings of medium spiny neurons (MSNs) in the NAc and determined the role of GSK3β in spike timing-dependent long-term potentiation (tLTP) in the chronic unpredictable mild stress (CUMS) mouse model of depression. To assess the specific role of GSK3β in tLTP, we used in vivo genetic silencing by an adeno-associated viral vector (AAV2) short hairpin RNA against GSK3β. In addition, we examined the role of the voltage-gated potassium Kv4.2 subunit, a molecular determinant of A-type K+currents, as a potential downstream target of GSK3β. We found increased levels of active GSK3β and augmented tLTP in CUMS mice, a phenotype that was prevented by selective GSK3β knockdown. Furthermore, knockdown of GSK3β in the NAc ameliorated depressive-like behavior in CUMS mice. Electrophysiological, immunohistochemical, biochemical, and pharmacological experiments revealed that inhibition of the Kv4.2 channel through direct phosphorylation at Ser-616 mediated the GSK3β-dependent tLTP changes in CUMS mice. Our results identify GSK3β regulation of Kv4.2 channels as a molecular mechanism of MSN maladaptive plasticity underlying depression-like behaviors and suggest that the GSK3β–Kv4.2 axis may be an attractive therapeutic target for MDD.

Sodium Butyrate Functions as an Antidepressant and Improves Cognition with Enhanced Neurotrophic Expression in Models of Maternal Deprivation and Chronic Mild Stress

2014 ◽  
Vol 11 (4) ◽  
pp. 359-366 ◽  
Author(s):  
Samira Valvassori ◽  
Roger Varela ◽  
Camila Arent ◽  
Gustavo Dal-Pont ◽  
Tamara Bobsin ◽  
...  
Keyword(s):  
Sodium Butyrate ◽  
Chronic Mild Stress ◽  
Maternal Deprivation ◽  
Mild Stress

Behavior and oxidative stress parameters in rats subjected to the animal's models induced by chronic mild stress and 6-hydroxydopamine

2021 ◽  
Vol 406 ◽  
pp. 113226
Author(s):  
Talita Tuon ◽  
Sandra S. Meirelles ◽  
Airam B. de Moura ◽  
Thayse Rosa ◽  
Laura A. Borba ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Oxidative Stress Parameters ◽  
6 Hydroxydopamine ◽  
And Oxidative Stress ◽  
Stress Parameters
Sign in / Sign up

Export Citation Format

Share Document