Differential cortical neurotrophin and cytogenetic adaptation after voluntary exercise in normal and amnestic rats.
Voluntary exercise (VEx) has profound effects on neural and behavioral plasticity, including recovery of CNS trauma and disease. However, the unique regional cortical adaption to VEx has not been elucidated. In a series of experiments, we first examined whether VEx would restore and retain neurotrophin levels in several cortical regions (frontal cortex [FC], retrosplenial cortex [RSC], occipital cortex [OC]) in an animal model (pyrithiamine-induced thiamine deficiency [PTD]) of the amnestic disorder Wernicke-Korsakoff syndrome. In addition, we assessed the time-dependent effect of VEx to rescue performance on a spontaneous alternation task. Following 2-weeks of VEx or stationary housing conditions (Stat), rats were behaviorally tested and brains were harvested either the day after VEx (24-h) or after an additional 2-week period (2-wk). In both control pair-fed (PF) rats and PTD rats, all neurotrophin levels (brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF], and vascular endothelial growth factor) increased at the 24-h period after VEx in the FC and RSC, but not OC. Two-weeks following VEx, BDNF remained elevated in both FC and RSC, whereas NGF remained elevated in only the FC. Interestingly, VEx only recovered cognitive performance in amnestic rats when there was an additional 2-wk adaptation period after VEx. Given this unique temporal profile, Experiment 2 examined the cortical cytogenetic responses in all three cortical regions following a 2-wk adaptation period after VEx. In healthy (PF) rats, VEx increased the survival of progenitor cells in both the FC and RSC, but only increased oligodendrocyte precursor cells (OLPs) in the FC. Furthermore, VEx had a selective effect of only recovering OLPs in the FC in PTD rats. These data reveal the therapeutic potential of exercise to restore cortical plasticity in the amnestic brain, and that the FC is one of the most responsive cortical regions to VEx.
Behavioral Neuroscience Program, Department of Psychology, Binghamton University-State University of New York, United States.
J M
JM
Hall
Behavioral Neuroscience Program, Department of Psychology, Binghamton University-State University of New York, United States.
R P
RP
Vetreno
Behavioral Neuroscience Program, Department of Psychology, Binghamton University-State University of New York, United States. Electronic address: lsavage@binghamton.edu.
L M
LM
Savage
D000647:Amnesia / Q000503:physiopathology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002470:Cell Survival; D002540:Cerebral Cortex / Q000503:physiopathology*; D020732:Cytogenetic Analysis; D005625:Frontal Lobe / Q000503:physiopathology; D006799:Housing, Animal; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D009778:Occipital Lobe / Q000503:physiopathology; D009836:Oligodendroglia / Q000502:physiology; D011745:Pyrithiamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000502:physiology; D013832:Thiamine Deficiency / Q000503:physiopathology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D042461:Vascular Endothelial Growth Factor A; D011745:Pyrithiamine; D020932:Nerve Growth Factor
5′-bromo-2′-deoxyuridine; ACh; ANOVA; BDNF; BrdU; ELISA; FC; GFAP; HRP; IVD; NG2; NGF; OC; OLPs; PBS; PF; PFC; PTD; RSC; SSC; TBS; Tris HCl-buffered saline; VEGF; VEx; WKS; Wernicke–Korsakoff syndrome; acetylcholine; amnesia; analysis of variance; brain-derived neurotrophic factor; cortex; cytogenesis; enzyme-linked immunosorbent assay; exercise; frontal cortex; glial fibrillary acidic protein; growth factors; horseradish peroxidase; intraventricular distance; nerve growth factor; occipital cortex; oligodendrocyte precursor cells; pair-fed; phosphate-buffered saline; prefrontal cortex; proteoglycan neuron-glia 2 protein; pyrithiamine-induced thiamine deficiency; retrosplenial cortex; saline-sodium citrate; vascular endothelial growth factor; voluntary exercise