title: Lack of exercise, via hindlimb suspension, impedes endogenous neurogenesis.
abstract: Bedridden patients who receive good physical rehabilitation are able to exhibit clinical improvement. Accumulating evidence demonstrates that exercise increases endogenous neurogenesis and may even protect against central nervous system (CNS) disorders. Here, we explored the effects of lack of exercise on neurogenesis in rats by employing a routine hindlimb suspension (HS) model over a 2-week period, which consists of elevating their tails, thereby raising their hindlimbs above the ground and unloading the weights in these extremities. In addition, the effects of exercise and recovery time with normal caging after HS were also explored. BrdU (50 mg/kg, i.p.) was injected every 8 h over the last 4 days of each paradigm to label proliferative cells. Immunohistochemical results revealed that HS significantly reduced the number of BrdU/Doublecortin double-positive cells in the subventricular zone and dentate gyrus. Exercise and recovery time significantly improved atrophy of the soleus muscle, but did not attenuate the HS-induced decrement in BrdU/Dcx-positive cells. A separate cohort of animals was exposed to the same HS paradigm and enzyme-linked immunosorbent assay (ELISA) of neurotrophic factors was performed on brain tissue samples harvested at the end of the HS period, as well as plasma samples from all animals. ELISA results revealed that HS reduced the levels of brain-derived neurotrophic factor in the hippocampus and vascular endothelial growth factor plasma levels. This study revealed that lack of exercise reduced neurogenesis with downregulation of neurotrophic factors. The use of the HS model in conjunction with CNS disease models should further elucidate the role of exercise in neurogenesis and neurotrophic factors in neurologic disorders.
authors.affiliation: Department of Neurology, Medical College of Georgia, Augusta, GA USA. tyasu37@cc.okayama-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Yasuhara
authors.forename: K
authors.initials: K
authors.lastname: Hara
authors.forename: M
authors.initials: M
authors.lastname: Maki
authors.forename: N
authors.initials: N
authors.lastname: Matsukawa
authors.forename: H
authors.initials: H
authors.lastname: Fujino
authors.forename: I
authors.initials: I
authors.lastname: Date
authors.forename: C V
authors.initials: CV
authors.lastname: Borlongan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D015536:Down-Regulation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D019417:Hindlimb Suspension; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D023421:Models, Animal; D009043:Motor Activity / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; D009479:Neuropeptides; D001973:Bromodeoxyuridine; D003345:Corticosterone