Molecular mechanisms underlying physical exercise-induced brain BDNF overproduction

Abstract

Accumulating evidence supports that physical exercise (EX) is the most effective non-pharmacological strategy to improve brain health. EX prevents cognitive decline associated with age and decreases the risk of developing neurodegenerative diseases and psychiatric disorders. These positive effects of EX can be attributed to an increase in neurogenesis and neuroplastic processes, leading to learning and memory improvement. At the molecular level, there is a solid consensus to involve the neurotrophin brain-derived neurotrophic factor (BDNF) as the crucial molecule for positive EX effects on the brain. However, even though EX incontestably leads to beneficial processes through BDNF expression, cellular sources and molecular mechanisms underlying EX-induced cerebral BDNF overproduction are still being elucidated. In this context, the present review offers a summary of the different molecular mechanisms involved in brain’s response to EX, with a specific focus on BDNF. It aims to provide a cohesive overview of the three main mechanisms leading to EX-induced brain BDNF production: the neuronal-dependent overexpression, the elevation of cerebral blood flow (hemodynamic hypothesis), and the exerkine signaling emanating from peripheral tissues (humoral response). By shedding light on these intricate pathways, this review seeks to contribute to the ongoing elucidation of the relationship between EX and cerebral BDNF expression, offering valuable insights into the potential therapeutic implications for brain health enhancement.

Anchoring Protein Increases Cerebrovascular Responses and Blood Pressure During Hypertension: Turn Round Quick and Start to Run

“…In summary, physical activity has been described as one of the most effective nonpharmacological approaches to lower blood pressure and prevent cardiovascular disease and deficits in brain function. 15 The current study supports the concept that exercise has beneficial effects on elements of vascular biology and blood pressure. The findings suggest such protection may be mediated, in part, via effects on AKAP150-dependent protein interactions and signaling.…”

Impact of Exercise Intensity on Cerebral BDNF Levels: Role of FNDC5/Irisin

“…The crucial role of BDNF in the positive effects of EX on the brain [24][25][26] is well established, as in animal studies, anti-BDNF strategies reversed the cognitive benefits associated with EX [5,27,28], while in humans, the val66met polymorphism associated with a defect in activity-dependent regulated BDNF secretion, attenuated the cognitive benefits of EX [29][30][31]. While neuronal activity via calcium influx and neurotransmitter release and hemodynamic pathway through elevation of cerebral blood flow have long been considered as dominant mechanisms to increase cerebral BDNF expression [32], the humoral/endocrine pathway has recently been reported to play a considerable role in cerebral BDNF production in both rodents and humans [12], highlighting muscle FNDC5 production and irisin secretion [15].…”

Aerobic exercise alters DNA hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsy

“…BDNF has strongly been linked to epilepsy during epileptogenesis as well as influencing excitability and connectivity in the adult brain [48] , [49] , [50] . Additionally, BDNF has been shown to increase in response to exercise [20] , [51] , while studies have also shown that BDNF expression can vary depending on the exercise intensity and type [21] , [52] . Serum IL-6 is a pro-inflammatory cytokine typically present at low levels in the brain but can be increased with seizures [53] .…”