<scp>AdipoRon</scp> 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.