Nerve Growth Factor Is Responsible for Exercise-Induced Recovery of Septohippocampal Cholinergic Structure and Function

• Published in: Frontiers in Neuroscience
• Main Authors: Joseph M. Hall, Fernando Gomez-Pinilla, Lisa M. Savage
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-11-01
• Subjects: NGF; BDNF; acetylcholine; exercise; basal forebrain; hippocampus
• Online Access: https://www.frontiersin.org/article/10.3389/fnins.2018.00773/full

Exercise has been shown to improve or rescue cognitive functioning in both humans and rodents, and the augmented actions of neurotrophins within the hippocampus and associated regions play a significant role in the improved neural plasticity. The septohippocampal circuit is modified by exercise. Beyond an enhancement of spatial working memory and a rescue of hippocampal activity-dependent acetylcholine (ACh) efflux, the re-emergence of the cholinergic/nestin neuronal phenotype within the medial septum/diagonal band (MS/dB) is observed following exercise (Hall and Savage, 2016). To determine which neurotrophin, brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF), is critical for exercise-induced cholinergic improvements, control and amnestic rats had either NGF or BDNF sequestered by TrkA-IgG or TrkB-IgG coated microbeads placed within the dorsal hippocampus. Hippocampal ACh release within the hippocampus during spontaneous alternation was measured and MS/dB cholinergic neuronal phenotypes were assessed. Sequestering NGF, but not BDNF, abolished the exercise-induced recovery of spatial working memory and ACh efflux. Furthermore, the re-emergence of the cholinergic/nestin neuronal phenotype within the MS/dB following exercise was also selectively dependent on the actions of NGF. Thus, exercise-induced enhancement of NGF within the septohippocampal pathway represents a key avenue for aiding failing septo-hippocampal functioning and therefore has significant potential for the recovery of memory and cognition in several neurological disorders.