Intranasal administration of exosomes derived from adipose mesenchymal stem cells ameliorates depressive-like behaviors and inhibits inflammation via AMPK/mTOR-mediated autophagy.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Major depressive disorder (MDD) is a severe, and often treatment-resistant, psychiatric disorder. Mesenchymal stem cell-derived exosomes have been shown to be neuroprotective. Here we employed adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) as a novel therapeutic approach for depressive-like behavior in mice and explored the underlying mechanisms. ADSC-Exos were administered intranasally to mice subjected to chronic restraint stress to assess behavioral changes and neuroprotection in terms of apoptosis, AMPK-mTOR signaling, and NLRP3 pathway activation by western blotting, microglial activation by immunofluorescence, and changes in serum inflammatory factors by ELISA. The effects of ADSC-Exos were also studied in vitro in HT22 cells. ADSC-Exos significantly improved depressive-like behavior, anxiety-like behavior, and cognitive function in mice. ADSC-Exos had significant neuroprotective effects, including reducing neuronal apoptosis and promoting autophagy by activating AMPK-mTOR signaling, ultimately reducing neuroinflammation. In vitro, ADSC-Exos inhibited corticosterone-induced apoptosis, activated autophagy in an AMPK pathway-dependent manner, and inhibited NLRP3 inflammasome activation. ADSC-Exos may be a potential treatment for MDD by alleviating depressive-like behaviors and protecting against tissue injury, possibly through activation of AMPK-mTOR signaling a

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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