TY - JOUR
T1 - Long-term exercise pre-training attenuates Alzheimer’s disease–related pathology in a transgenic rat model of Alzheimer’s disease
AU - Yang, Luodan
AU - Wu, Chongyun
AU - Li, Yong
AU - Dong, Yan
AU - Wu, Celeste Yin Chieh
AU - Lee, Reggie Hui Chao
AU - Brann, Darrell W.
AU - Lin, Hung Wen
AU - Zhang, Quanguang
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to American Aging Association.
PY - 2022/6
Y1 - 2022/6
N2 - Alzheimer’s disease (AD) is the most common form of dementia. Despite enormous efforts around the world, there remains no effective cure for AD. This study was performed to investigate the effects of long-term exercise pretreatment on the typical pathology of AD in a novel transgenic AD rat model. Male 2-month-old animals were divided into the following groups: wild-type (WT) rats, AD rats, and AD rats with treadmill exercise pretreatment (AD-Exe). After exercise pretreatment, the Barnes maze task, passive avoidance task, and cued fear conditioning test were performed to test learning and memory function. The elevated plus maze, open field test, sucrose preference test, and forced swim test were conducted to measure anxious-depressive–like behavior. Immunofluorescence staining, Golgi staining, transmission electron microscopy, Western blot analysis, F-Jade C staining, TUNEL staining, and related assay kits were conducted to measure Aβ plaques, tau hyperphosphorylation, neuronal damage, neuronal degeneration, dendritic spine density, synapses, synaptic vesicles, mitochondrial morphology, mitochondrial dynamic, oxidative stress, and neuroinflammation. Behavioral tests revealed that long-term exercise pretreatment significantly alleviated learning and memory dysfunction and anxious-depressive–like behaviors in AD animals. In addition, exercise pretreatment attenuated amyloid-β deposition and tau hyperphosphorylation and preserved spine density, synapses, and presynaptic vesicles. Exercise also inhibited neuronal damage, neuronal apoptosis, and neuronal degeneration. Additional studies revealed the imbalance of mitochondrial dynamics was significantly inhibited by exercise pretreatment accompanied by a remarkable suppression of oxidative stress and neuroinflammation. Our findings suggest that long-term exercise pretreatment alleviated behavioral deficits and typical pathologies of the AD rat model, supporting long-term exercise pretreatment as a potential approach to delay the progression of AD.
AB - Alzheimer’s disease (AD) is the most common form of dementia. Despite enormous efforts around the world, there remains no effective cure for AD. This study was performed to investigate the effects of long-term exercise pretreatment on the typical pathology of AD in a novel transgenic AD rat model. Male 2-month-old animals were divided into the following groups: wild-type (WT) rats, AD rats, and AD rats with treadmill exercise pretreatment (AD-Exe). After exercise pretreatment, the Barnes maze task, passive avoidance task, and cued fear conditioning test were performed to test learning and memory function. The elevated plus maze, open field test, sucrose preference test, and forced swim test were conducted to measure anxious-depressive–like behavior. Immunofluorescence staining, Golgi staining, transmission electron microscopy, Western blot analysis, F-Jade C staining, TUNEL staining, and related assay kits were conducted to measure Aβ plaques, tau hyperphosphorylation, neuronal damage, neuronal degeneration, dendritic spine density, synapses, synaptic vesicles, mitochondrial morphology, mitochondrial dynamic, oxidative stress, and neuroinflammation. Behavioral tests revealed that long-term exercise pretreatment significantly alleviated learning and memory dysfunction and anxious-depressive–like behaviors in AD animals. In addition, exercise pretreatment attenuated amyloid-β deposition and tau hyperphosphorylation and preserved spine density, synapses, and presynaptic vesicles. Exercise also inhibited neuronal damage, neuronal apoptosis, and neuronal degeneration. Additional studies revealed the imbalance of mitochondrial dynamics was significantly inhibited by exercise pretreatment accompanied by a remarkable suppression of oxidative stress and neuroinflammation. Our findings suggest that long-term exercise pretreatment alleviated behavioral deficits and typical pathologies of the AD rat model, supporting long-term exercise pretreatment as a potential approach to delay the progression of AD.
KW - Alzheimer’s disease
KW - Amyloid-β deposition
KW - Memory
KW - Mitochondrial dynamics
KW - TgF344-AD rats
KW - Treadmill exercise
UR - http://www.scopus.com/inward/record.url?scp=85125354209&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85125354209&partnerID=8YFLogxK
U2 - 10.1007/s11357-022-00534-2
DO - 10.1007/s11357-022-00534-2
M3 - Article
C2 - 35229257
AN - SCOPUS:85125354209
SN - 2509-2715
VL - 44
SP - 1457
EP - 1477
JO - GeroScience
JF - GeroScience
IS - 3
ER -