Possible Involvement of Signal Transducers and Activators of Transcription 3 System on Depression in the Model Mice Brain

Abstract

Although available evidence from neurobiological studies consistently indicates that depression phenotypes are the outcome of a combination of genetic and environmental factors, 1,2) little is known about the pathophysiology of depression. A large number of clinical observations have suggested that stress is a predisposing factor involved in the onset of affective disorders, especially depression. [3][4][5] Most animal models of depression are based on behavioral deficits induced by a variety of stress paradigms. One of the most commonly used animal models of depression is a learned helplessness (LH) paradigm. In this paradigm, animals previously exposed to inescapable shock are subsequently less able to escape from shock than control animals. Animals with LH behavior exhibit impairments of behavioral, biochemical, physiological and hormonal parameters somewhat similar to those observed in patients with depressive disorders for several days.2,6-8) Interestingly, however, only 10-80% of animals exposed to inescapable shock develop LH behaviors. [9][10][11] The variability of responses in these animals may be due to several factors including procedures and condition of the induction of LH behaviors, the criteria used for defining LH behaviors 11) and also genetic variation. When we think about the variation from another viewpoint, clarifying the reason for this may give us information about endogenous factors that are involved in generation of depressive disorders. Therefore, in this article, we divided stressed animals into two groups which presented a symptom of depression and which did not show it, artificially, and examined the gene expression changes between.We previously found that antidepressant drugs and a traditional Chinese and Japanese prescription (Wakan-yaku) with antidepressant-like action enhances expression of BCL2/adenovirus E1B 19kD-interacting protein 3 (BNIP3) mRNA in a cultured cell line NG108-15. Our results suggest that BNIP3 is a candidate intrinsic factor related to antidepressive effects of these drugs.12) We also found that BNIP3 mRNA expression is upregulated by stress exposure and BNIP3 may be involved in imipramine-induced amelioration of depressive state of LH mouse brain.13) Using this model animal brain, it seems possible to find novel depressive factors in addition to BNIP-3.Microarray technology vastly improved brain research when it arrived some years ago and has become a very useful tool for identification of genes and molecular pathways involved in psychiatric disorders. [14][15][16] Further to understand the pathophysiology of depression, accumulation of gene expression analyses based on the phenotypic variability of animals exposed to stress is needed. In the present study, we investigated the expression of genes associated with the pathogenesis of depressive disorders using DNA microarray technique in the LH mice frontal cortex. Genes that were down-regulated or up-regulated were examined in detail by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR...

Yueju Pill Rapidly Induces Antidepressant-Like Effects and Acutely Enhances BDNF Expression in Mouse Brain

“…The procedures for learned helplessness were followed as reported [15, 16]. Learned helplessness experiments were performed in soundproofed two-way shuttle boxes (40 × 10 × 13 cm), with walls made of clear Plexiglas.…”

Wuling powder prevents the depression-like behavior in learned helplessness mice model through improving the TSPO mediated-mitophagy

“…Control animals underwent the same handling without receiving the e-shock, and named Control group (Li et al, 2006;Mingmalairak et al, 2010;Peruga et al, 2011). The equipment was cleaned with 75% ethanol during the course of experiment.…”

Behavioral Stress-Induced Activation of FoxO3a in the Cerebral Cortex of Mice

“…Serotonin has been shown to increase FoxO3a phosphorylation by activating brain Akt (30), which could mask IES-responsive signals that lead to activation of FoxO3a at an early post-IES period. Despite being an acute stress, IES-induced biological changes in brain may last for several days (58,59), such as differentially changing the levels of neurotrophins (58), down-regulating signal transducers activators of transcription 3 (Stat3)-interacting protein (StIP1), up-regulating the suppressor of cytokine signaling 3 (Socs3) (60), and elevating the immediate early gene nerve growth factor-inducible gene A (NGFI-A) (59). The robust increase in FoxO3a activity on post-IES day-3 and day-8 highly suggests that there are FoxO3a-regulating machineries responsible for the prolonged activation of FoxO3a, and this study focused on identifying the underlying mechanism.…”