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 journalArticle

2 Citations (Scopus)

Abstract

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
Volume50
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Streptozocin
Exercise
Alzheimer Disease
Antioxidants
Cytokines
Hippocampal CA1 Region
Control Groups
Gliosis
Short-Term Memory
Amyloid
Fluorescent Antibody Technique
Sprague Dawley Rats
Hippocampus
Proteins
Cell Death
Western Blotting
Enzyme-Linked Immunosorbent Assay
Apoptosis
Staining and Labeling
Gene Expression

Keywords

  • COGNITION IMPROVEMENT
  • INFLAMMATION
  • NEUROPROTECTION
  • OXIDATIVE STRESS
  • PREEXERCISE

ASJC Scopus subject areas

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

Cite this

Beneficial Effects of Exercise Pretreatment in a Sporadic Alzheimer's Rat Model. / Wu, Chongyun; Yang, Luodan; Tucker, Donovan; Dong, Yan; Zhu, Ling; Duan, Rui; Liu, Timon Cheng Yi; Zhang, Quanguang.

In: Medicine and Science in Sports and Exercise, Vol. 50, No. 5, 01.05.2018, p. 945-956.

Research output: Contribution to journalArticle

Wu, Chongyun ; Yang, Luodan ; Tucker, Donovan ; Dong, Yan ; Zhu, Ling ; Duan, Rui ; Liu, Timon Cheng Yi ; Zhang, Quanguang. / Beneficial Effects of Exercise Pretreatment in a Sporadic Alzheimer's Rat Model. In: Medicine and Science in Sports and Exercise. 2018 ; Vol. 50, No. 5. pp. 945-956.
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abstract = "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.",
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AU - Duan, Rui

AU - Liu, Timon Cheng Yi

AU - Zhang, Quanguang

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N2 - 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.

AB - 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.

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KW - OXIDATIVE STRESS

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