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

Joseph M Hall,Fernando Gomez-Pinilla,Lisa M Savage

doi:10.3389/fnins.2018.00773

Joseph M Hall, Fernando Gomez-Pinilla + Show 1 more

Open Access

https://doi.org/10.3389/fnins.2018.00773

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Abstract

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.

Highlights

Exercise improves an array of health outcomes, including the enhancement of learning and memory, under pathological conditions
An initial experiment was conducted to ensure that the microbead procedures could inhibit available nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) for an extended time period
Whereas bilateral hippocampal implantation of TrkAIgG microbeads was more effective at reducing available NGF than unilateral implantation of TrkA-IgG microbeads [F(1,10) = 4.54, p = 0.045, see Figure 3C], this was not the case for of the implantation of TrkB-IgG microbeads, as unilateral and bilateral implantation did not differ in reducing available BDNF [F(1,8) = 0.058, p = 0.816], similar to previous studies indicating that injection of unilateral TrkB-IgG microbeads are sufficient to reduce BDNF levels in the HPC

Summary

Introduction

Exercise improves an array of health outcomes, including the enhancement of learning and memory, under pathological conditions. Brain-derived neurotrophic factor (BDNF) is considered to play an essential role in mediating the pro-cognitive effects of exercise via the enhancement of hippocampal neurogenesis, dendritic complexity, and synaptic plasticity (Vaynman et al, 2004; Stranahan et al, 2007; Wrann et al, 2013; Vivar and van Praag, 2017). Nerve growth factor (NGF) is essential for normal development as well as the NGF Regulates Exercise-Induced ACh Recovery functioning of mature cholinergic neurons in the basal forebrain. In preclinical models of neurological disease, NGF treatment reverses the effects of lesions and agerelated degeneration of basal forebrain cholinergic neurons, including the recovery of learning and memory (Tuszynski and Blesch, 2004)

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