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 Chronic Mild Stress Modulates Activity-Dependent Transcription of BDNF in Rat Hippocampal Slices

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Raffaella Molteni ◽  
Andrea C. Rossetti ◽  
Elisa Savino ◽  
Giorgio Racagni ◽  
Francesca Calabrese
Keyword(s):  
Intracellular Signaling ◽  
Ex Vivo ◽  
Hippocampal Slices ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Mrna Levels ◽  
Bdnf Expression ◽  
Bdnf Mrna ◽  
Activity Dependent ◽  
Bdnf Transcription

Although activity-dependent transcription represents a crucial mechanism for long-lasting experience-dependent changes in the hippocampus, limited data exist on its contribution to pathological conditions. We aim to investigate the influence of chronic stress on the activity-dependent transcription of brain-derived neurotrophic factor (BDNF). Theex vivomethodology of acute stimulation of hippocampal slices obtained from rats exposed to chronic mild stress (CMS) was used to evaluate whether the adverse experience may alter activity-dependent BDNF gene expression. CMS reduces BDNF expression and that acute depolarization significantly upregulates total BDNF mRNA levels only in control animals, showing that CMS exposure may alter BDNF transcription under basal conditions and during neuronal activation. Moreover, while the basal effect of CMS on total BDNF reflects parallel modulations of all the transcripts examined, isoform-specific changes were found after depolarization. This different effect was also observed in the activation of intracellular signaling pathways related to the neurotrophin. In conclusion, our study discloses a functional alteration of BDNF transcription as a consequence of stress. Being the activity-regulated transcription a critical process in synaptic and neuronal plasticity, the different regulation of individual BDNF promoters may contribute to long-lasting changes, which are fundamental for the vulnerability of the hippocampus to stress-related diseases.

scholarly journals Haloperidol and aripiprazole impact on the BDNF and glucocorticoid receptor levels in the rat hippocampus and prefrontal cortex: effect of the chronic mild stress

2021 ◽  
Vol 55 (3) ◽  
pp. 153-162
Author(s):  
Jana Osacka ◽  
Romana Koprdova ◽  
Andrej Tillinger ◽  
Zdenko Pirnik ◽  
Alexander Kiss
Keyword(s):  
Prefrontal Cortex ◽  
Weight Gain ◽  
Glucocorticoid Receptor ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Typical Antipsychotic ◽  
Mrna Levels ◽  
Frozen Sections ◽  
Bdnf Mrna ◽  
The Brain

Abstract Objective. Changes in the brain derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC) and hippocampus (HIP) are associated with psychiatric diseases and stress response. Chronic mild stress (CMS) may alter BDNF as well as GR levels in both the PFC and the HIP. The aim of the present study was to find out whether chronic treatment with a typical antipsychotic haloperidol (HAL) and an atypical antipsychotic aripiprazole (ARI) may modify the CMS effect on the BDNF and GR expression in the above-mentioned structures. Methods. The rats were exposed to CMS for 3 weeks and from the 7th day of CMS injected with vehicle (VEH), HAL (1 mg/kg) or ARI (10 mg/kg) for 4 weeks. BDNF and GR mRNA levels were established in the PFC and the HIP by Real Time PCR, whereas, PFC and HIP samples were obtained by punching them from 500 µm thick frozen sections. C-Fos immunoreactivity was analyzed in the PFC and the HIP on 30 µm thick paraformaldehyde fixed sections. Weight gain and corticosterone (CORT) levels were also measured. Results. The CMS and HAL suppressed the BDNF and GR mRNA levels in the PFC. In the HIP, CMS elevated BDNF mRNA levels that were suppressed by HAL and ARI treatments. The CMS decreased the c-Fos immunoreactivity in the PFC in both HAL- and ARI-treated animals. In the HIP, HAL increased the c-Fos immunoreactivity that was again diminished in animals exposed to CMS. Stressed animals gained markedly less weight until the 7th day of CMS, however, later their weight gain did not differ from the unstressed ones or was even higher in CMS+HAL group. Un-stressed HAL and ARI animals gained less weight than the VEH ones. Neither CMS nor HAL/ARI affected the plasma CORT levels. Conclusion. The present data indicate that HAL and ARI in the doses 1 mg/kg or 10 mg/kg, respectively, does not modify the effect of the CMS preconditioning on the BDNF and GR mRNA levels in the PFC or the HIP. However, HAL seems to modify the CMS effect on the HIP activation.

scholarly journals Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus

2018 ◽  
Vol 115 (15) ◽  
pp. E3549-E3558 ◽  
Author(s):  
John Marshall ◽  
Xiao-zhong Zhou ◽  
Gang Chen ◽  
Su-qing Yang ◽  
Ya Li ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Adaptor Protein ◽  
Chronic Mild Stress ◽  
Mapk Signaling ◽  
Mild Stress ◽  
Limbic Structure ◽  
Double Knockout ◽  
Bdnf Expression ◽  
Functional Studies

Stress-related alterations in brain-derived neurotrophic factor (BDNF) expression, a neurotrophin that plays a key role in synaptic plasticity, are believed to contribute to the pathophysiology of depression. Here, we show that in a chronic mild stress (CMS) model of depression the Gαi1 and Gαi3 subunits of heterotrimeric G proteins are down-regulated in the hippocampus, a key limbic structure associated with major depressive disorder. We provide evidence that Gαi1 and Gαi3 (Gαi1/3) are required for the activation of TrkB downstream signaling pathways. In mouse embryonic fibroblasts (MEFs) and CNS neurons, Gαi1/3 knockdown inhibited BDNF-induced tropomyosin-related kinase B (TrkB) endocytosis, adaptor protein activation, and Akt–mTORC1 and Erk–MAPK signaling. Functional studies show that Gαi1 and Gαi3 knockdown decreases the number of dendrites and dendritic spines in hippocampal neurons. In vivo, hippocampal Gαi1/3 knockdown after bilateral microinjection of lentiviral constructs containing Gαi1 and Gαi3 shRNA elicited depressive behaviors. Critically, exogenous expression of Gαi3 in the hippocampus reversed depressive behaviors in CMS mice. Similar results were observed in Gαi1/Gαi3 double-knockout mice, which exhibited severe depressive behaviors. These results demonstrate that heterotrimeric Gαi1 and Gαi3 proteins are essential for TrkB signaling and that disruption of Gαi1 or Gαi3 function could contribute to depressive behaviors.

Minocycline protects against oxidative damage and alters energy metabolism parameters in the brain of rats subjected to chronic mild stress

2014 ◽  
Vol 30 (2) ◽  
pp. 545-553 ◽  
Author(s):  
Gislaine Z. Réus ◽  
Helena M. Abelaira ◽  
Amanda L. Maciel ◽  
Maria Augusta B. dos Santos ◽  
Anelise S. Carlessi ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Oxidative Damage ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
The Brain

β-Carboline harmine reverses the effects induced by stress on behaviour and citrate synthase activity in the rat prefrontal cortex

2013 ◽  
Vol 25 (6) ◽  
pp. 328-333 ◽  
Author(s):  
Helena Mendes Abelaira ◽  
Gislaine Zilli Réus ◽  
Giselli Scaini ◽  
Emilio Luiz Streck ◽  
José Alexandre Crippa ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Energy Metabolism ◽  
Citrate Synthase ◽  
Memory Performance ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Sucrose Intake ◽  
The Brain

ObjectivesThe present study was aimed at evaluating the effects of the administration of β-carboline harmine on behaviour and citrate synthase activity in the brain of rats exposed to chronic mild stress (CMS) procedure.MethodsTo this aim, after 40 days of exposure to CMS procedure, rats were treated with harmine (15 mg/kg/day) for 7 days, then memory, anhedonia and citrate synthase activity were assessed.ResultOur findings demonstrated that stressed rats treated with saline increased the sucrose intake, and the stressed rats treated with harmine reversed this effect. Neither stress nor harmine treatment altered memory performance in rats. In addition, chronic stressful situations induced increase in citrate synthase activity in the prefrontal cortex, but not in the hippocampus and striatum. Treatment with harmine reversed the increase in citrate synthase activity in the prefrontal cortex.ConclusionThese findings support the hypothesis that harmine could be involved in controlling the energy metabolism.

Chinese medicine Banxia-houpu decoction regulates c-fos expression in the brain regions in chronic mild stress model in rats

2004 ◽  
Vol 18 (3) ◽  
pp. 200-203 ◽  
Author(s):  
Weiyun Zhang ◽  
Jianmei Li ◽  
Jixiao Zhu ◽  
Zhenqiu Shi ◽  
Yong Wang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Chronic Mild Stress ◽  
Brain Regions ◽  
Mild Stress ◽  
Stress Model ◽  
Fos Expression ◽  
The Brain

scholarly journals Microstructural and Metabolic Recovery of Anhedonic Rat Brains: An In Vivo Diffusion MRI and 1H-MRS Approach

Data ◽  
2018 ◽  
Vol 3 (3) ◽  
pp. 29 ◽  
Author(s):  
Ahmad Khan ◽  
Sune Jespersen ◽  
Ove Wiborg ◽  
Christopher Kroenke ◽  
Brian Hansen
Keyword(s):  
Diffusion Mri ◽  
Imaging System ◽  
Chronic Mild Stress ◽  
Ventral Hippocampus ◽  
Control Group ◽  
Mild Stress ◽  
1H Mrs ◽  
Unpredictable Chronic Mild Stress ◽  
The Brain

This article presents longitudinal 1H-MR Spectroscopy (1H-MRS) data from ventral hippocampus and in vivo diffusion MRI (dMRI) data of the brain from control and anhedonic rats. The 1H-MRS and dMRI data were acquired using a 9.4 T preclinical imaging system. Before MRI experiments, animals were exposed to unpredictable chronic mild stress exposure for eight weeks and on the basis of a sucrose consumption test were identified as anhedonic and resilient. An age-matched group of animals, unexposed to the unpredictable chronic mild stress paradigm was considered as control. Data was acquired at the age of 18, 20 and 25 weeks in the anhedonic group and at the age of 18 and 22 weeks in the control group. This multimodal MRI data provides metabolic information of ventral hippocampus and dMRI based microstructural parameters of the brain.

scholarly journals The Changes of Expression and Methylation of Genes Involved in Oxidative Stress in Course of Chronic Mild Stress and Antidepressant Therapy with Agomelatine

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 644
Author(s):  
Paulina Wigner ◽  
Ewelina Synowiec ◽  
Paweł Jóźwiak ◽  
Piotr Czarny ◽  
Michał Bijak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitrosative Stress ◽  
Mononuclear Cells ◽  
Methylation Status ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Oxidative And Nitrosative Stress ◽  
Peripheral Blood Mononuclear ◽  
Taqman Gene Expression Assay ◽  
The Brain

Preclinical studies conducted so far suggest that oxidative stress processes may be associated with the mechanism of depression development. This study shows the effects of chronic administration of agomelatine on expression and the methylation status of Sod1, Sod2, Gpx1, Gpx4, Cat, Nos1, and Nos2 in the brain stricture and blood in the chronic mild stress (CMS) animal model of depression. The animals were exposed to the CMS procedure and treatment with agomelatine (10 mg/kg/day, IP) for five weeks and then were sacrificed. TaqMan Gene Expression Assay, Western blot, and methylation-sensitive high-resolution melting techniques were used to evaluate mRNA and protein expression of the genes, and the methylation status of their promoters. Gpx1, Gpx4, and Sod2 expression in the PBMCs and Sod1 and Sod2 expression in the brain were reduced in the stressed group after agomelatine administration. CMS caused an increase in the methylation of the third Gpx4 promoter in peripheral blood mononuclear cells and Gpx1 promoter in the cerebral cortex. Additionally, stressed rats treated with agomelatine displayed a significantly lower Gpx4 level in the hypothalamus. The results confirm the hypothesis that the CMS procedure and agomelatine administration change the expression level and methylation status of the promoter region of genes involved in oxidative and nitrosative stress.

P.1.003 Inflammatory response in the brain of rats exposed to chronic mild stress

2013 ◽  
Vol 23 ◽  
pp. S5-S6
Author(s):  
C. Zecchillo ◽  
F. Macchi ◽  
R. Molteni ◽  
G. Racagni ◽  
M. Papp ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
The Brain
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