title: Moderate Treadmill Exercise Protects Synaptic Plasticity of the Dentate Gyrus and Related Signaling Cascade in a Rat Model of Alzheimer's Disease.
abstract: The dentate gyrus (DG) of the hippocampus is known to be more resistant to the effects of various external factors than other hippocampal areas. This study investigated the neuroprotective effects of moderate treadmill exercise on early-phase long-term potentiation (E-LTP) and its molecular signaling pathways in the DG of amyloid β rat model of sporadic Alzheimer's disease (AD). Animals were preconditioned to run on treadmill for 4 weeks and concurrently received ICV infusion of Aβ₁₋₄₂ peptides (250 pmol/day) during the third and fourth weeks of exercise training. We utilized in vivo electrophysiological recordings to assess the effect of exercise and/or AD pathology on basal synaptic transmission and E-LTP magnitude of the perforant pathway synapses in urethane-anesthetized rats. Immunoblotting analysis was used to quantify changes in the levels of learning and memory-related key signaling molecules. The AD-impaired basal synaptic transmission and suppression of E-LTP in the DG were prevented by prior moderate treadmill exercise. In addition, exercise normalized the basal levels of memory and E-LTP-related signaling molecules including Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), calcineurin (PP2B), and brain-derived neurotrophic factor (BDNF). Exercise also prevented the reduction of phosphorylated CaMKII and aberrant increase of PP2B seen after E-LTP induction in amyloid-infused rats. Our data suggests that by restoring the balance of kinase-phosphatase, 4 weeks of moderate treadmill exercise prevents DG synaptic deficits and deleterious alterations in signaling pathways associated with AD.
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. kalkadhi@uh.edu.
authors.forename: Karim A
authors.initials: KA
authors.lastname: Alkadhi
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D019703:Calcineurin / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D018891:Dentate Gyrus / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005081:Exercise Therapy; D006801:Humans; D017774:Long-Term Potentiation; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity; D010446:Peptide Fragments / Q000633:toxicity; D019580:Perforant Pathway / Q000502:physiology; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D012420:Running / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019703:Calcineurin
keywords: Alzheimer’s disease; BDNF; Basal synaptic transmission; Early LTP; Memory; Treadmill exercise