AdipoRon Mitigates Anxiety and Depression Symptoms in Chronic Sleep-Restricted Mice via Modulation of Neuroinflammatory Responses.

The contemporary lifestyle has resulted in an epidemic of chronic sleep restriction (SR), which has emerged as a substantial contributor to mood disorders, particularly anxiety and depression. This study examined the effectiveness of AdipoRon (Adipo), a synthetic adiponectin agonist, in mitigating anxious behaviours and depression-like symptoms in a chronic SR mice model. Forty male Swiss albino mice were divided into four groups: wide platform (WP), SR, SR + melatonin (Mel), and SR + Adipo. Over 21 days, the animals underwent a modified multiple-platform technique to induce SR, followed by daily intranasal treatments. The open field test and elevated plus maze were conducted to assess anxiety-related behaviours, while the forced swimming test and sucrose splash test were used to assess depressive symptoms. Serum corticosterone concentrations, a marker of microglia activation, and pro-inflammatory mediators (NF-кB and IL-1β) in the prefrontal cortex (PFC) were also examined. Intranasal administration of Adipo markedly decreased anxiety-like behaviours, despair, and apathy in sleep-restricted mice compared to the SR group. Adipo therapy also reduced pro-inflammatory proteins and ionised calcium-binding adaptor molecule-1 (Iba-1)-positive cells in the PFC and restored serum corticosterone levels. These outcomes emphasise the therapeutic benefit of Adipo as an alternative therapy for mood disorders associated with SR.