Treadmill Running Improves Spatial Learning Memory Through Inactivation Of Nuclear Factor Kappa B/Mitogen-Activated Protein Kinase Signaling Pathway In Amyloid-Beta-Induced Alzheimer Disease Rats

Purpose: Exercise is known to reduce proinflammatory cytokines production and apoptosis. We investigated the effect of treadmill running on spatial learning memory in terms of activation of nuclear factor kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) signaling pathway in Alzheimer disease (AD) rats. We also evaluated the effect of treadmill running on proinflammatory cytokine production and apoptosis.Methods: Using the stereotaxic frame, amyloid-beta (A beta) was injected into the lateral ventricle of the brain. The rats belong to treadmill running groups were forced to run on a motorized treadmill for 30 minutes per a day during 4 weeks, starting 3 days after A beta injection. Morris water maze task was done for the determination of spatial learning memory. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry for cleaved caspase-3, and western blot for NF-kappa B, inhibitory protein of NF-kappa B (I kappa B), MAPK signaling pathway, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta were done.Results: Induction of AD increased proinflammatory cytokine secretion by activating the NF-kappa B/MAPK signaling pathway. These changes induced apoptosis in the hippocampus and reduced spatial learning memory. In contrast, treadmill running inactivated the NF-kappa B/MAPK signaling pathway and suppressed proinflammatory cytokine production. These changes inhibited apoptosis and improved spatial learning memory.Conclusions: Current results showed that treadmill running promoted spatial learning memory through suppressing proinflammatory cytokine production and apoptosis via inactivation of NF-kappa B/MAPK signaling pathway. Treadmill exercise can be considered an effective intervention for symptom relieve of AD.