title: Exercise leads to the re-emergence of the cholinergic/nestin neuronal phenotype within the medial septum/diagonal band and subsequent rescue of both hippocampal ACh efflux and spatial behavior.
abstract: Exercise has been shown to improve cognitive functioning in a range of species, presumably through an increase in neurotrophins throughout the brain, but in particular the hippocampus. The current study assessed the ability of exercise to restore septohippocampal cholinergic functioning in the pyrithiamine-induced thiamine deficiency (PTD) rat model of the amnestic disorder Korsakoff Syndrome. After voluntary wheel running or sedentary control conditions (stationary wheel attached to the home cage), PTD and control rats were behaviorally tested with concurrent in vivo microdialysis, at one of two time points: 24-h or 2-weeks post-exercise. It was found that only after the 2-week adaption period did exercise lead to an interrelated sequence of events in PTD rats that included: (1) restored spatial working memory; (2) rescued behaviorally-stimulated hippocampal acetylcholine efflux; and (3) within the medial septum/diagonal band, the re-emergence of the cholinergic (choline acetyltransferase [ChAT+]) phenotype, with the greatest change occurring in the ChAT+/nestin+ neurons. Furthermore, in control rats, exercise followed by a 2-week adaption period improved hippocampal acetylcholine efflux and increased the number of neurons co-expressing the ChAT and nestin phenotype. These findings demonstrate a novel mechanism by which exercise can modulate the mature cholinergic/nestin neuronal phenotype leading to improved neurotransmitter function as well as enhanced learning and memory.
authors.affiliation: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, State University of New York, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Hall
authors.affiliation: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, State University of New York, United States. Electronic address: lsavage@binghamton.edu.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Savage
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000963:Antimetabolites / Q000633:toxicity; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D005081:Exercise Therapy; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D020932:Nerve Growth Factor / Q000378:metabolism; D064231:Nestin / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D011745:Pyrithiamine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000502:physiology; D020665:Septum of Brain / Q000473:pathology*; D013037:Spatial Behavior / Q000502:physiology*; D013832:Thiamine Deficiency / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation*; D013997:Time Factors
chemical_list: D000963:Antimetabolites; D019208:Brain-Derived Neurotrophic Factor; D064231:Nestin; D011745:Pyrithiamine; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine
keywords: Acetylcholine; BDNF; Diagonal band; Exercise; Medial Septum; NGF; Nestin
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