Exercise-mediated muscle-hypothalamus crosstalk: Improvement for cognitive dysfunction caused by disrupted circadian rhythm

In contemporary societal evolution, the increasing disruption of the natural sleep-wake cycle, attributable to factors such as shift work and overexposure to artificial light, has been paralleled by a marked escalation in the incidence of cognitive impairments and the prevalence of neurodegenerative diseases. Current management strategies for cognitive impairments include pharmacological and non-pharmacological interventions. Pharmacological interventions for cognitive impairments typically involve medications to manage cognitive symptoms and improve neurological functions. However, these drugs show limited long-term efficacy in slowing disease progression and may cause side effects. Given the widespread occurrence of cognitive dysfunction, it is crucial to develop accessible non-pharmacological interventions. Physical activity and exercise have emerged as pivotal lifestyle determinants known to exert a modulatory effect on the risk profile for cognitive dysfunction caused by disrupted circadian rhythms. The skeletal muscle, a dynamic tissue, undergoes a profound morphological and metabolic reconfiguration in response to physical exertion, along with the secretion of myokines. Additionally, the hypothalamus, particularly the ventromedial nuclei, arcuate nuclei, and the suprachiasmatic nucleus, have crucial functions in regulating physical activity, influencing energy metabolism, and managing circadian cycles. Nevertheless, the communication between the hypothalamus and skeletal muscle during exercise is not fully understood. This narrative review integrates current knowledge on the interaction between the hypothalamus and skeletal muscle during exercise, emphasizing its neuroendocrine effects and potential therapeutic implications for alleviating cognitive dysfunction associated with disrupted circadian rhythms.