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Treadmill Running Reverses Cognitive Declines due to Alzheimer Disease

CHO, JINKYUNG1; SHIN, MIN-KYOO2; KIM, DONGHYUN1; LEE, INHWAN1; KIM, SHINUK3; KANG, HYUNSIK1

Medicine & Science in Sports & Exercise: September 2015 - Volume 47 - Issue 9 - p 1814–1824
doi: 10.1249/MSS.0000000000000612
Basic Sciences

Purpose: This study investigated the effect of treadmill running on cognitive declines in the early and advanced stages of Alzheimer disease (AD) in 3xTg-AD mice.

Methods: At 4 months of age, 3xTg-AD mice (N = 24) were assigned to control (AD + CON, n = 12) or exercise (AD + EX, n = 12) group. At 24 months of age, 3xTg-AD mice (N = 16) were assigned to AD + CON (n = 8) or AD + EX (n = 8) group. The AD + EX mice were subjected to treadmill running for 12 wk. At each pathological stage, the background strain mice were included as wild-type control (WT + CON, n = 8–12).

Results: At the early stage of AD, 3xTg-AD mice had impaired short- and long-term memory based on Morris water maze along with higher cortical Aβ deposition, higher hippocampal and cortical tau pathology, and lower hippocampal and cortical PSD-95 and synaptophysin. A 12-wk treadmill running reversed the impaired cognitive declines and significantly improved the tau pathology along with suppression of the decreased PSD-95 and synaptophysin in the hippocampus and cortex. At the advanced stage of AD, 3xTg-AD mice had impaired short- and long-term memory along with higher levels of Aβ deposition, soluble Aβ1–40 and Aβ1–42, tau pathology, and lower levels of brain-derived neurotrophic factor, PSD-95, and synaptophysin in the hippocampus and cortex. A 12-wk treadmill running reversed the impaired cognitive declines and significantly improved the Aβ and tau pathology along with suppression of the decreased synaptic proteins and brain-derived neurotrophic factor in the hippocampus and cortex.

Conclusions: The current findings suggest that treadmill running provides a nonpharmacological means to combat cognitive declines due to AD pathology.

1College of Sport Science, Sungkyunkwan University, Suwon, REPUBLIC OF KOREA; 2Department of Biological Sciences, Sungkyunkwan University, Suwon, REPUBLIC OF KOREA; and 3College of Engineering, Sangmyung University, Cheonan, REPUBLIC OF KOREA

Address for correspondence: Hyunsik Kang, Ph.D., College of Sport Science, Sungkyunkwan University, 2066 Seobu-Ro, Jangan-Gu, Suwon, Gyeonggi-Do 440–746, Republic of Korea; E-mail: hkang@skku.edu.

Submitted for publication November 2014.

Accepted for publication January 2015.

© 2015 American College of Sports Medicine