Research . . . Inhibition of c-Jun stress-activated protein kinase activity improves depressive-like behavior.

Stress is an important factor leading to depression and other behavioral disorders.previous studies have shown that chronic stress can lead to neuroinflammation and increase the level of proinflammatory cytokines in the brain. The occurrence of psychological disorders such as depression and anxiety is related to the excessive increase of pro-inflammatory cytokines.c-Jun N-terminal kinase (JNK) is a class of kinases that play an important regulatory role in the inflammatory response, and is closely related to the development and diseases of the central nervous system.can regulating JNK activity limit the role of inflammatory factors and help prevent or treat depression? In order to answer this question, Zhang Juntao of Lin Wenjuan, Key Laboratory of mental health, Chinese Academy of Sciences, and other members of the research group used a rat model of depression caused by neuritis syndrome to systematically investigate the regulatory role of JNK in depressive behavior, and observed proinflammatory cytokines, JNK activity and glucocorticoid receptor (gluococ) in several brain regions closely related to depression Expression of phosphorylation (pgr-ser246) at the site of orticoid receptor (GR) 246.the results showed that central JNK was related to the occurrence and reversal of depressive behavior, and it was involved in the regulation of depression behavior caused by neuroinflammation, including loss of pleasure, autonomous activity, exploration behavior and despair behavior.neuroinflammation simultaneously increased JNK activity in multiple brain regions (such as habenula, amygdala, medial prefrontal lobe), increased the secretion of proinflammatory cytokines IL-1, IL-6 and TNF, and was accompanied by overexpression of glucocorticoid receptor pgr-ser246.and JNK inhibitor sp600125 can prevent JNK over activation caused by neuroinflammation, slow down or reverse depression like behavior (Fig. 1), and reverse the increase of proinflammatory cytokines and the over expression of glucocorticoid receptor 246 in the brain of depressed animals (Fig. 2).Figure 1: JNK inhibitor sp600125 reverses neuroinflammation induced depressive behavior (a, B, C, d) and hyperactivity of JNK phosphorylation proteins in habenula, amygdala and medial prefrontal cortex (E, f). Figure 2: JNK inhibitor sp600125 reverses the increase of inflammatory cytokines and overexpression of glucocorticoid receptor (GR) induced by neuroinflammation.TNF - α and IL-1 β (a, B, c) in habenula, amygdala and medial prefrontal cortex; glucocorticoid receptor GR and pgr-ser246 (D, e) these results suggest that JNK is involved in the regulation of inflammatory depression, and its mechanism involves its interaction with pro-inflammatory cytokines and phosphorylation of gr-ser246.it provides a new insight into the pathogenesis of depression and suggests that inhibiting the activity of c-jun stress activated protein kinase may be a new strategy for the treatment of depression.the research was funded by the National Natural Science Foundation of China and the Key Laboratory of mental health, Chinese Academy of Sciences. The results were published in Psychoneuroendocrinology.paper information: Zhang, j.t., Lin, W.J., Tang, M.M., Zhao, Y., Zhang, K., Wang, x.q., Li, Y.C. (2020) Inhibition of JNK ameliorates depressive-like behaviors and reduces the activation of pro-inflammatory cytokines and the phosphorylation of glucocorticoid receptors at serine 246 induced by neuroinflammation. Psychoneuroendocrinology，113:154080.doi.org/10 1016 / j.psyneuen.2019.104580 source: Key Laboratory of mental health, Chinese Academy of Sciences Lin Wenjuan research group