The effects of exercise on hypothalamic neurodegeneration of Alzheimer's disease mouse model
Khoa Do,Brenton Thomas Laing,Taylor Landry,Wyatt Bunner,Naderi Mersaud,Tomoko Matsubara,Peixin Li,Yuan Yuan,Qun Lu,Hu Huang +9 more
TLDR
The results indicated that early onset of metabolic abnormalities may contribute to the pathology of AD, which is associated with increased inflammation as well as decreased neuronal population and key neuropeptides in the hypothalamus, and a hypothalamic-mediated mechanism where exercise prevents the progression of dementia and of Alzheimer's disease.Abstract:
Alzheimer's disease is a neurodegenerative disorder that affects the central nervous system. In this study, we characterized and examined the early metabolic changes in the triple transgenic mouse AD model (3xtg-AD), and their relationship with the hypothalamus, a key regulator of metabolism in the central nervous system. We observed that the 3xtg-AD model exhibited significantly higher oxygen consumption as well as food intake before reported amyloid plaque formation, indicating that metabolic abnormalities occurred at early onset in the 3xtg-AD model compared with their counterparts. Analysis of gene expression in the hypothalamus indicated increased mRNA expression of inflammation- and apoptosis-related genes, as well as decreased gene expression of Agouti-related protein (AgRP) and Melanocortin 4 receptor (MC4R) at 12 weeks of age. Immunofluorescence analysis revealed that pro-opiomelanocortin (POMC) and NPY-expressing neurons decreased at 24 weeks in the 3xtg-AD model. Four weeks of voluntary exercise were sufficient to reverse the gene expression of inflammation and apoptotic markers in the hypothalamus, six weeks of exercise improved glucose metabolism, moreover, 8 weeks of voluntary exercise training attenuated apoptosis and augmented POMC and NPY-expressing neuronal populations in the hypothalamus compared to the control group. Our results indicated that early onset of metabolic abnormalities may contribute to the pathology of AD, which is associated with increased inflammation as well as decreased neuronal population and key neuropeptides in the hypothalamus. Furthermore, early intervention by voluntary exercise normalized hypothalamic inflammation and neurodegeneration as well as glucose metabolism in the 3xtg-AD model. The data, taken as a whole, suggests a hypothalamic-mediated mechanism where exercise prevents the progression of dementia and of Alzheimer's disease.read more
Citations
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Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's diseases
TL;DR: In this article, the authors used TgCRND8 mice to examine directly the interaction between exercise and the AD cascade, and found that five months of voluntary exercise resulted in a decrease in extracellular amyloid-β (Aβ) plaques in the frontal cortex.
Journal ArticleDOI
Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease
Estella A. Newcombe,Judith Camats-Perna,Mallone L. Silva,Nicholas Valmas,Tee Jong Huat,Rodrigo Medeiros +5 more
TL;DR: The different inflammatory signals associated with AD and its risk factors will be outlined to demonstrate how chronic inflammation may be influencing individual susceptibility to AD.
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Mitochondria as Potential Targets in Alzheimer Disease Therapy: An Update.
Giovanna Cenini,Wolfgang Voos +1 more
TL;DR: A detailed analysis of the significance of mitochondrial deterioration in AD and of a pharmacological treatment at this level is performed, as an effective drug treatment in AD is still missing and new therapeutic concepts are urgently needed.
Journal ArticleDOI
Physical Activity and Brain Health
TL;DR: The potential mechanisms underlying the effects of PA on brain health are discussed, focusing on hormones, neurotrophins, and neurotransmitters, the release of which is modulated by PA, as well as on the intra- and extra-cellular pathways that regulate the expression of some of the genes involved.
Journal ArticleDOI
Environment and Gene Association With Obesity and Their Impact on Neurodegenerative and Neurodevelopmental Diseases.
TL;DR: The obesogenic environmental conditions, the genes, and the interaction gene–environment would lead to a better understanding of the etiology of these diseases.
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