Potential role of apelin in mediating the antidepressant effects of physical exercise

Sarcopenia is muscle ageing condition comprising progressive decline in muscle strength, mass and function. Epidemiology data have shown that sarcopenia is highly associated with depression in geriatric patients, suggesting an impact of skeletal muscle on brain health. However, the mechanisms underlying this muscle-brain crosstalk resulting in depression is yet to be explored. Apelin, a novel myokine linked to sarcopenia, can elicit antidepressant effects and influence hippocampal neuroplasticity in rodent studies. By using a mouse model of depression induced by chronic unpredictable stress (CUS), a study conducted by PhD Student Mr Yu Jia Sui from Dr Suk-yu Yau’s team at Hong Kong Polytechnic university discovered that stressed mice showed significantly decreased protein expression of apelin and its receptor (APJ) in the hippocampus, whereas 4-weeks voluntary wheel running exercise rescued depression-like behaviour in association with increased Apelin/APJ levels in the hippocampus and lower limb muscles including gastrocnemius (Gas), and tibialis anterior (TA) of stressed mice. Specific knockout of Apelin in skeletal muscle attenuated the antidepressant effect of voluntary exercise, suggesting the key role of apelin in mediating the antidepressant effect of physical exercise, whereas overexpression of apelin in Gas and TA muscles mimicked antidepressant effects of physical exercise. These data suggest that the potential role of apelin mediating the crosstalk of the muscle-brain axis on sarcopenia-associated depression, and provide a novel potential therapeutic target for treating geriatric depression.