Possible Involvement of the IL-6/JAK2/STAT3 Pathway in the Hypothalamus in Depressive-Like Behavior of Rats Exposed to Chronic Mild Stress

Abstract

<b><i>Introduction:</i></b> The interleukin-6/janus kinase 2/signal transducer and activator of transcription 3 (IL-6/JAK2/STAT3) pathway plays an important role in immune function, but little research has focused on this pathway in depression. We sought to examine the relationship between the IL-6/JAK2/STAT3 pathway and depressive-like behavior. <b><i>Methods:</i></b> Using a chronic mild stress (CMS) paradigm, a total of 36 adult male Sprague-Dawley rats were divided into four matched groups: (1) control + vehicle, (2) CMS + vehicle, (3) control + paroxetine, and (4) CMS + paroxetine. We investigated the effects of CMS on depressive-like behavior by using the forced swimming test (FST). Subsequently, the mRNA levels of members of the IL-6/JAK2/STAT3 pathway were assessed by qRT-PCR. <b><i>Results:</i></b> We found that rats exposed to CMS displayed a significant increase in immobility time and a decrease in climbing time in the FST. Moreover, mRNA levels of IL-6, JAK2, and STAT3 in the hypothalamus were increased following CMS. We also found that mRNA levels of IL-6, JAK2, and STAT3 were normalized by paroxetine administration, which coincided with normalization of the depressive-like behavior. <b><i>Conclusions:</i></b> The IL-6/JAK2/STAT3 pathway may be activated in depression, and targeting this pathway may provide a novel effective therapeutic approach for the treatment of depression.

Guggulsterone Mediated JAK/STAT and PPAR-Gamma Modulation Prevents Neurobehavioral and Neurochemical Abnormalities in Propionic Acid-Induced Experimental Model of Autism

“…Likewise, the prior study found an enhanced depressed effect following PPA treatment [ 85 ]. According to previous findings, interleukin-6 elevates STAT3 levels and promotes depression by increasing serotonin transporters (SERT) [ 86 , 87 ]. The increased inflammatory cascade suggested by neurochemical analysis of brain homogenate and blood plasma could contribute to the increased inflammatory reactions.…”

The Circadian Rhythms of STAT3 in the Rat Pineal Gland and Its Involvement in Arylalkylamine-N-Acetyltransferase Regulation

“…STAT3, however, plays an important role in a wide range of physiological functions, including neurogenesis, energy homeostasis, hormonal regulation, and synaptic plasticity [ 13 ]. Despite STAT3 expression being well described in various brain systems [ 18 , 19 , 20 , 21 , 22 ], there is little evidence of its expression in the pineal gland and none is placed in context with its function. Our previous work described the circadian rhythms in Stat3 gene expression and endogenous and LPS-induced STAT3 protein phosphorylation in the SCN.…”

Artesunate regulates the proliferation and differentiation of neural stem cells by activating the JAK‑2/STAT‑3 signaling pathway in ischemic stroke

“…IL-6 is an important inflammatory factor that promotes the phosphorylation of STAT-3 protein through JAK-2 (43). The IL-6/JAK-2/STAT-3 signaling pathway has been reported to be involved in various diseases, including tumors, ulcerative colitis, hyperuricemic nephropathy and chronic mild stress (44)(45)(46)(47). In the present study, IL-6 was used to activate the JAK-2/STAT-3 signaling pathway.…”