Brain‐derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition

TLDR

BDNF is known to mediate exercise‑induced improvements in synaptic plasticity and cognition, likely through interactions with energy‑metabolism pathways. This study investigated how voluntary exercise alters hippocampal expression of energy‑regulation and cognition‑related molecules in rats and assessed BDNF’s contribution to these changes. One week of voluntary exercise upregulated AMPK, uMtCK, UCP2, BDNF, IGF‑I, and ghrelin, with BDNF levels correlating with the others; blocking BDNF eliminated the exercise‑enhanced spatial learning and disrupted these molecular associations, indicating BDNF functions as a metabotrophin linking energy metabolism to synaptic plasticity.

Abstract

Abstract Brain‐derived neurotrophic factor (BDNF) has been shown to mediate the effects of exercise on synaptic plasticity and cognitive function, in a process in which energy metabolism probably plays an important role. The purpose of the present study was to examine the influence of exercise on rat hippocampal expression of molecules involved in the regulation of energy management and cognitive function, and to determine the role of BDNF in these events. One week of voluntary exercise that enhanced learning and memory performance elevated the expression of molecular systems involved in the metabolism of energy [AMP‐activated protein kinase (AMPK), ubiquitous mitochondrial creatine kinase (uMtCK) and uncoupling protein 2] and molecules that work at the interface of energy and synaptic plasticity [BDNF, insulin‐like growth factor I (IGF‐I) and ghrelin]. The levels of BDNF mRNA were associated with the mRNA levels of AMPK, uMtCK, IGF‐I and ghrelin. Inhibiting the action of BDNF during exercise abolished an exercise‐mediated enhancement in spatial learning and increased the expression of all of the molecular systems studied. BDNF blocking also disrupted the association between learning speed and levels of AMPK, uMtCK, ghrelin and IGF‐I mRNAs. These findings suggest that the effects of exercise on synaptic plasticity and cognitive function involve elements of energy metabolism, and that BDNF seems to work at the interface between the two processes as a metabotrophin.