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Moderate Treadmill Exercise Protects Synaptic Plasticity of the Dentate Gyrus and Related Signaling Cascade in a Rat Model of Alzheimer's Disease.
- Source :
-
Molecular neurobiology [Mol Neurobiol] 2015 Dec; Vol. 52 (3), pp. 1067-1076. Date of Electronic Publication: 2014 Oct 08. - Publication Year :
- 2015
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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.
- Subjects :
- Alzheimer Disease physiopathology
Amyloid beta-Peptides toxicity
Animals
Brain-Derived Neurotrophic Factor biosynthesis
Calcineurin metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism
Excitatory Postsynaptic Potentials physiology
Humans
Long-Term Potentiation
Male
Nerve Tissue Proteins metabolism
Peptide Fragments toxicity
Perforant Pathway physiology
Phosphorylation
Protein Processing, Post-Translational
Rats
Rats, Wistar
Running physiology
Signal Transduction physiology
Alzheimer Disease therapy
Dentate Gyrus physiopathology
Exercise Therapy
Neuronal Plasticity
Physical Conditioning, Animal physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1182
- Volume :
- 52
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 25288155
- Full Text :
- https://doi.org/10.1007/s12035-014-8916-1