title: Comparison of the Effect of Exercise on Late-Phase LTP of the Dentate Gyrus and CA1 of Alzheimer's Disease Model.
abstract: We investigated the neuroprotective effect of regular treadmill exercise training on long-term memory and its correlate: the late-phase long-term potentiation (L-LTP) and plasticity- and memory-related signaling molecules in the DG and CA1 areas of a rat model of Alzheimer's disease (AD) (i.c.v. infusion of Aβ1-42peptides, 2 weeks, 250 pmol/day). Testing in the radial arm water maze revealed severe impairment of spatial long-term memory in Aβ-infused sedentary rats but not in exercised Aβ-infused rats. The L-LTP, measured as changes in the field (f)EPSP and in the amplitude of population spike (pspike), was induced by multiple high-frequency stimulation in the CA1 and DG areas of anesthetized rats. The L-LTP of fEPSP in both areas was severely impaired in the sedentary Aβ rats but not in exercised Aβ rats. However, L-LTP of the pspike was severely suppressed in the CA1 area but not in the DG of sedentary Aβ rats. Immunoblot analysis revealed no increase in the levels of phosphorylated (p)-CREB, CaMKIV, and brain-derived neurotrophic factor (BDNF) in both CA1 and DG areas of sedentary Aβ rats during L-LTP, whereas the levels of these molecules were robustly increased in exercised Aβ rats. Impairment of synaptic function may be due to deleterious changes in the molecular signaling cascades that mediate synaptic structural and functional changes. The protective effect of regular exercise can be a promising therapeutic measure for countering or delaying the AD-like pathology.
authors.affiliation: Department of PPS, College of Pharmacy, University of Houston, Houston, TX, 77204-5037, USA.
authors.forename: An T
authors.initials: AT
authors.lastname: Dao
authors.affiliation: Department of PPS, College of Pharmacy, University of Houston, Houston, TX, 77204-5037, USA.
authors.forename: Munder A
authors.initials: MA
authors.lastname: Zagaar
authors.affiliation: Department of PPS, College of Pharmacy, University of Houston, Houston, TX, 77204-5037, USA.
authors.forename: Amber T
authors.initials: AT
authors.lastname: Levine
authors.affiliation: Department of PPS, College of Pharmacy, University of Houston, Houston, TX, 77204-5037, USA. KAlkadhi@uh.edu.
authors.forename: Karim A
authors.initials: KA
authors.lastname: Alkadhi
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000473:pathology / Q000503:physiopathology*; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D010805:Physical Conditioning, Animal; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4
keywords: Alzheimer’s disease; BDNF; CA1 area; CaMKIV; Dentate gyrus; Exercise; In vivo population spike recording; L-LTP; Learning; Long-term memory; Radial arm water maze; fEPSP