scholarly journals Chronic Lithium Treatment Affects Anxious Behaviors and theExpression of Serotonergic Genes in Midbrain Raphe Nuclei of Defeated Male Mice

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1293
Author(s):  
Dmitry A. Smagin ◽  
Irina L. Kovalenko ◽  
Anna G. Galyamina ◽  
Irina V. Belozertseva ◽  
Nikolay V. Tamkovich ◽  
...  
Keyword(s):  
Lithium Treatment ◽  
Social Defeat ◽  
Raphe Nuclei ◽  
Male Mice ◽  
Social Defeat Stress ◽  
Agonistic Interactions ◽  
Chronic Social Defeat Stress ◽  
Partition Test ◽  
Midbrain Raphe Nuclei ◽  
Raphé Nuclei

There is experimental evidence that chronic social defeat stress is accompanied by the development of an anxiety, development of a depression-like state, and downregulation of serotonergic genes in midbrain raphe nuclei of male mice. Our study was aimed at investigating the effects of chronic lithium chloride (LiCl) administration on anxiety behavior and the expression of serotonergic genes in midbrain raphe nuclei of the affected mice. A pronounced anxiety-like state in male mice was induced by chronic social defeat stress in daily agonistic interactions. After 6 days of this stress, defeated mice were chronically treated with saline or LiCl (100 mg/kg, i.p., 2 weeks) during the continuing agonistic interactions. Anxiety was assessed by behavioral tests. RT-PCR was used to determine Tph2, Htr1a, Htr5b, and Slc6a4 mRNA expression. The results revealed anxiolytic-like effects of LiCl on social communication in the partition test and anxiogenic-like effects in both elevated plus-maze and social interaction tests. Chronic LiCl treatment upregulated serotonergic genes in midbrain raphe nuclei. Thus, LiCl effects depend on the treatment mode, psycho-emotional state of the animal, and experimental context (tests). It is assumed that increased expression of serotonergic genes is accompanied by serotonergic system activation and, as a side effect, by higher anxiety.

Effects of chronic lithium treatment on anxious behaviors and serotonergic genes expression in the midbrain raphe nuclei in defeated male mice

2021 ◽  
Author(s):  
Dmitry A. Smagin ◽  
Irina L. Kovalenko ◽  
Anna G. Galyamina ◽  
Irina V. Belozertseva ◽  
Nikolay V. Tamkovich ◽  
...  
Keyword(s):  
Lithium Treatment ◽  
Raphe Nuclei ◽  
Male Mice ◽  
Genes Expression ◽  
Plus Maze ◽  
Partition Test ◽  
Midbrain Raphe Nuclei ◽  
Licl Treatment ◽  
Raphé Nuclei ◽  
And Function

AbstractThere are experimental data that mixed anxiety/depression-like state induced by chronic social defeat stress is accompanied by development of anxiety and downregulation of serotonergic gene expression in the midbrain raphe nuclei of male mice. The paper aimed to study the effect of chronic lithium chloride (LiCl) on anxious behaviors and the expression of serotonergic genes (Tph2, Slc6a4, Htr1a, Htr5b) in the midbrain raphe nuclei of defeated mice. Slight anxiolytic effects of LiCl were found on the commucativeness in the partition test, and anxiogenic-like effects, estimated by the elevated plus-maze and social interactions tests. Chronic LiCl treatment induced overexpression of the serotonergic genes in the midbrain raphe nuclei of defeated mice. We can assume that effects of LiCl, rather anxiogenic, may be due to activation of serotonergic system induced by hyperexpression of serotonergic genes. Our findings will allow to understand the factors involved in the positive and side effects of lithium on anxiety and function of serotonergic genes which are involved into mechanisms of depression.

Downregulation of Serotonergic Gene Expression in the Raphe Nuclei of the Midbrain Under Chronic Social Defeat Stress in Male Mice

2013 ◽  
Vol 48 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Ul’yana A. Boyarskikh ◽  
Natalya P. Bondar ◽  
Maxim L. Filipenko ◽  
Natalia N. Kudryavtseva
Keyword(s):  
Gene Expression ◽  
Social Defeat ◽  
Raphe Nuclei ◽  
Male Mice ◽  
Social Defeat Stress ◽  
Chronic Social Defeat Stress ◽  
Raphé Nuclei

scholarly journals Dysfunction in Ribosomal Gene Expression in the Hypothalamus and Hippocampus following Chronic Social Defeat Stress in Male Mice as Revealed by RNA-Seq

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Dmitry A. Smagin ◽  
Irina L. Kovalenko ◽  
Anna G. Galyamina ◽  
Anatoly O. Bragin ◽  
Yuriy L. Orlov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Social Stress ◽  
Ribosome Biogenesis ◽  
Social Defeat ◽  
Brain Regions ◽  
Ribosomal Gene ◽  
Rna Seq ◽  
Male Mice ◽  
Social Defeat Stress ◽  
Chronic Social Defeat Stress

Chronic social defeat stress leads to the development of anxiety- and depression-like states in male mice and is accompanied by numerous molecular changes in brain. The influence of 21-day period of social stress on ribosomal gene expression in five brain regions was studied using the RNA-Seq database. MostRps, Rpl, Mprs, andMprlgenes were upregulated in the hypothalamus and downregulated in the hippocampus, which may indicate ribosomal dysfunction following chronic social defeat stress. There were no differentially expressed ribosomal genes in the ventral tegmental area, midbrain raphe nuclei, or striatum. This approach may be used to identify a pharmacological treatment of ribosome biogenesis abnormalities in the brain of patients with “ribosomopathies.”

Changes in the expression of dopaminergic genes in brain structures of male mice exposed to chronic social defeat Stress: An RNA-seq study

2016 ◽  
Vol 50 (1) ◽  
pp. 161-163 ◽  
Author(s):  
I. L. Kovalenko ◽  
D. A. Smagin ◽  
A. G. Galyamina ◽  
Yu. L. Orlov ◽  
N. N. Kudryavtseva
Keyword(s):  
Social Defeat ◽  
Brain Structures ◽  
Rna Seq ◽  
Male Mice ◽  
Social Defeat Stress ◽  
Chronic Social Defeat Stress ◽  
Dopaminergic Genes

scholarly journals Chronic stress impairs male spermatogenesis function and nectin-3 protein expression in the testis

2020 ◽  
pp. 297-306
Author(s):  
T. Li ◽  
J. Yao ◽  
Q. Zhang ◽  
Q. Li ◽  
J. Li ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Molecular Mechanisms ◽  
Social Defeat ◽  
Histological Structure ◽  
Male Mice ◽  
Corticotropin Releasing Hormone ◽  
Social Defeat Stress ◽  
Control Male ◽  
Releasing Hormone ◽  
Chronic Social Defeat Stress

Chronic stress is a crucial public issue that occurs when a person is repetitively stimulated by various stressors. Previous researches have reported that chronic stress induces spermatogenesis dysfunction in the reproductive system, but its molecular mechanisms remain unclear. The nectin protein family, including nectin-1 to nectin-4, is Ca(2+)-independent immunoglobulin-like cell adhesion molecules, that are widely expressed in the hippocampus, testicular tissue, epithelial cells and other sites. Nectin-3 contributes to the sperm development at the late stage, and the abnormal expression of nectin-3 impairs spermatogenesis. Some recent studies have demonstrated that stress induces a decrease in nectin-3 expression in the hippocampus via corticotropin-releasing hormone (CRH) to corticotropin-releasing hormone receptor 1 (CRHR1) pathway. Here, we tested whether chronic stress also caused a reduction in nectin-3 expression in the testis. We established a chronic social defeat stress paradigm, which provides naturalistic and complex chronic stress in male C57BL/6 mice. After 25 days of chronic social defeat stress, the mice showed weight loss, thymic atrophy and some other typical symptoms of chronic stress (e.g. anxiety-like behavior and social avoidance behavior). We found gonad atrophy, testicular histological structure changes and semen quality reductions in the stressed mice. The stressed male mice significantly spent more time to impregnate the female mice than the control male mice. Moreover, nectin-3 protein levels in stressed mice were significantly decreased in the testes compared with those in control mice. In addition, we found that the CRHR1 expression level was increased in the testes of stressed mice. Therefore, we demonstrated a decreased level of nectin-3 expression and an increase in CRHR1 expression in the testis after exposure to chronic stress, which may provide a potential therapeutic target for the spermatogenesis dysfunction induced by chronic stress.

scholarly journals Chronic social defeat stress impairs goal-directed behavior through dysregulation of ventral hippocampal activity in male mice

2021 ◽  
Author(s):  
Keitaro Yoshida ◽  
Michael R. Drew ◽  
Anna Kono ◽  
Masaru Mimura ◽  
Norio Takata ◽  
...  
Keyword(s):  
Social Withdrawal ◽  
Social Defeat ◽  
Task Completion ◽  
Male Mice ◽  
Social Defeat Stress ◽  
Motivated Behavior ◽  
Hippocampal Activity ◽  
Chronic Social Defeat Stress ◽  
Food Seeking ◽  
Goal Directed Behavior

AbstractChronic stress is a risk factor for a variety of psychiatric disorders, including depression. Although impairments to motivated behavior are a major symptom of clinical depression, little is known about the circuit mechanisms through which stress impairs motivation. Furthermore, research in animal models for depression has focused on impairments to hedonic aspects of motivation, whereas patient studies suggest that impairments to appetitive, goal-directed motivation contribute significantly to motivational impairments in depression. Here, we characterized goal-directed motivation in repeated social defeat stress (R-SDS), a well-established mouse model for depression in male mice. R-SDS impaired the ability to sustain and complete goal-directed behavior in a food-seeking operant lever-press task. Furthermore, stress-exposed mice segregated into susceptible and resilient subpopulations. Interestingly, susceptibility to stress-induced motivational impairments was unrelated to stress-induced social withdrawal, another prominent effect of R-SDS in mouse models. Based on evidence that ventral hippocampus (vHP) modulates sustainment of goal-directed behavior, we monitored vHP activity during the task using fiber photometry. Successful task completion was associated with suppression of ventral hippocampal neural activity. This suppression was diminished after R-SDS in stress-susceptible but not stress-resilient mice. The serotonin selective reuptake inhibitor (SSRI) escitalopram and ketamine both normalized vHP activity during the task and restored motivated behavior. Furthermore, optogenetic vHP inhibition was sufficient to restore motivated behavior after stress. These results identify vHP hyperactivity as a circuit mechanism of stress-induced impairments to goal-directed behavior and a putative biomarker that is sensitive to antidepressant treatments and that differentiates susceptible and resilient individuals.

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