Exercise-induced neuroplasticity Molecular mechanisms and implications for cognitive health and disease intervention
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This review synthesizes recent advances in elucidating the molecular basis underlying the effects of exercise on neuroplasticity. Specifically, we will focus on how exercise induces changes in neural connectivity at different levels of organization through conserved signalling pathways mediated by brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and dopamine, which differentially modulate region-specific synaptic plasticity, neurogenesis, and large-scale brain network reorganization. Recent technological breakthroughs have enabled the exploration of cellular heterogeneity and circuit-level plasticity in the hippocampus and prefrontal cortex through single-cell sequencing and optogenetics following chronic and acute exercise interventions. Additionally, recent evidence suggests that the gut microbiota-brain axis plays a regulatory role in mediating the effects of exercise on neuroplasticity. Clinically, exercise interventions can mitigate the pathophysiology of neurodegenerative diseases (NDs), psychiatric disorders, and aid recovery after brain injury. In the future, we envision personalized exercise prescriptions based on individual molecular and phenotypic profiles as an emerging concept in the field of precision medicine. From an evolutionary perspective, the co-adaptation of physical activity and cognitive capacity highlights the adaptive significance of exercise-induced neuroplasticity. Through the integration of basic and clinical science, we hope this review will propel the field forward to new, more targeted, efficacious interventions.
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