Beneficial Effects of Exercise Pretreatment in a Sporadic Alzheimer's Rat Model

Chongyun Wu, Luodan Yang, Donovan Tucker, Yan Dong, Ling Zhu, Rui Duan, Timon Cheng Yi Liu, Quanguang Zhang

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


Purpose This study aimed to examine the effects of swimming exercise pretreatment on a streptozotocin (STZ)-induced sporadic Alzheimer's disease (AD) rat model and provide an initial understanding of related molecular mechanisms. Methods Male 2.5-month-old Sprague-Dawley rats were divided into the following four groups: (a) control, (b) swim + vehicle, (c) STZ without swim, and (d) swim + STZ. The Barnes maze task and novel object recognition test were used to measure hippocampus-dependent spatial learning and working memory, respectively. Immunofluorescence staining, Western blot analysis, enzyme-linked immunosorbent assay (ELISA) analysis, and related assay kits were used to assess synaptic proteins, inflammatory cytokines, total antioxidant capacity, antioxidant enzymes, amyloid-beta production, and tau hyperphosphorylation. Results Behavioral tests revealed that exercise pretreatment could significantly inhibit STZ-induced cognitive dysfunction (P < 0.05). STZ animals displayed significant loss of presynaptic/postsynaptic markers in the hippocampal CA1 that was reversed by exercise pretreatment (P < 0.05). STZ rats also displayed increased reactive gliosis, release of proinflammatory cytokines, and oxidative damage, effects attenuated by preexercise (P < 0.05, between-treatment changes). Likewise, preexercise significantly induced protein expression (P < 0.001) and DNA-binding activity (P = 0.015) of Nrf2 and downstream antioxidant gene expression in the hippocampal CA1 region (P < 0.05). STZ rats had increased levels of amyloid-beta (1-42) and tau hyperphosphorylation that were significantly ameliorated by exercise (P < 0.05). Histological studies showed that exercise imparted substantial neuroprotection (P < 0.001), suppressing neuronal apoptosis-like cell death in the hippocampal CA1 compared with the STZ control group (P < 0.001). Conclusions Exercise pretraining exerts multifactorial benefits on AD that support its use as a promising new therapeutic option for prevention of neurodegeneration in the elderly and/or AD population.

Original languageEnglish (US)
Pages (from-to)945-956
Number of pages12
JournalMedicine and Science in Sports and Exercise
Issue number5
StatePublished - May 1 2018



ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation


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