Epilepsy and exercise: a narrative review on the crucial role of neurosteroids in modulating GABAergic neurotransmission

Abstract

Epilepsy is a disorder of the central nervous system (CNS) characterized by the onset of seizures that significantly worsens the independence and quality of life of people affected. Although significant progress has been obtained in the research and development of pharmacological approaches able to reduce the frequency of seizures, a significant number of patients with epilepsy remain drug-resistant, highlighting the need for further research aimed at understanding the physiological mechanisms underlying neuronal excitability. In this regard, neurosteroids have been identified as key molecules in neuronal excitability due to their ability to influence GABAergic transmission paving the way for studies and research to better understand their role in epileptic mechanisms. Interestingly, some evidence has shown that moderate to intense physical exercise can influence neurosteroid synthesis, such as allopregnanolone, pregnenolone and tetrahydrodeoxycorticosterone, suggesting a therapeutic potential for physical activity in the context of epilepsy. In fact, the most recent clinical evidence has prompted a re-evaluation of the role of exercise in epilepsy, shifting from a risk factor to a non-pharmacological tool able to improve cognition and quality of life in people with epilepsy. This narrative review of the literature focuses on the role of exercise as a positive modulator of neurosteroid synthesis, as crucial GABAergic modulators, and its use as a promising non-pharmacological strategy for epilepsy.