Exercise and its beneficial impacts on mood disorders and neurodegeneration: a novel mechanistic perspective of the exosomes involvement.

Mood disorders (MDs), including depression and anxiety, are among the leading causes of global disability, yet current treatments often yield incomplete remission. Women are disproportionately affected, underscoring the need for more targeted and effective interventions. Emerging evidence suggests that small extracellular vesicles (sEVs), particularly exosomes released during aerobic exercise, may mediate its antidepressant effects by facilitating inter-organ communication and delivering neuroactive cargo, such as microRNAs, across the blood-brain barrier. These vesicles influence synaptic plasticity, neurogenesis, and inflammation, offering both mechanistic insight and biomarker potential. This review proposes that exercise-induced exosomes are key modulators of brain health and mood regulation. By synthesizing findings from human and animal studies, we explore how aerobic exercise promotes neural resilience through exosomal signaling, with attention to sex-specific hormonal influences. Understanding these pathways may inform precision-based, non-pharmacological strategies for managing mood disorders and mitigating neurodegenerative risk.