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

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.

Automated summary

The study revealed that chronic mild stress exacerbates depressive-like behavior and activates the IL-6/JAK2/STAT3 pathway in the hypothalamus. Treatment with paroxetine in depressed rats normalized the mRNA levels of IL-6, JAK2, and STAT3, as well as the depressive behavior.