title: Early alterations in blood and brain RANTES and MCP-1 expression and the effect of exercise frequency in the 3xTg-AD mouse model of Alzheimer's disease.
abstract: Exercise has been shown to protect against cognitive decline and Alzheimer's disease (AD) progression, however the dose of exercise required to protect against AD is unknown. Recent studies show that the pathological processes leading to AD cause characteristic alterations in blood and brain inflammatory proteins that are associated with the progression of AD, suggesting that these markers could be used to diagnosis and monitor disease progression. The purpose of this study was to determine the impact of exercise frequency on AD blood chemokine profiles, and correlate these findings with chemokine brain expression changes in the triple transgenic AD (3xTg-AD) mouse model. Three month old 3xTg-AD mice were subjected to 12 weeks of moderate intensity wheel running at a frequency of either 1×/week or 3×/week. Blood and cortical tissue were analyzed for expression of monocyte chemotactic protein-1 (MCP-1) and regulated and normal T cell expressed and secreted (RANTES). Alterations in blood RANTES and MCP-1 expression were evident at 3 and 6 month old animals compared to WT animals. Three times per week exercise but not 1×/week exercise was effective at reversing serum and brain RANTES and MCP-1 expression to the levels of WT controls, revealing a dose dependent response to exercise. Analysis of these chemokines showed a strong negative correlation between blood and brain expression of RANTES. The results indicate that alterations in serum and brain inflammatory chemokines are evident as early signs of Alzheimer's disease pathology and that higher frequency exercise was necessary to restore blood and brain inflammatory expression levels in this AD mouse model.
authors.affiliation: Department of Physical Therapy, College of Allied Health Sciences, East Carolina University, 600 Moye Blvd. East Carolina University, Greenville, NC 27834, USA. Electronic address: haskinsm09@students.ecu.edu.
authors.forename: Morgan
authors.initials: M
authors.lastname: Haskins
authors.affiliation: Department of Physical Therapy, College of Allied Health Sciences, East Carolina University, 600 Moye Blvd. East Carolina University, Greenville, NC 27834, USA. Electronic address: joneste@ecu.edu.
authors.forename: Terry E
authors.initials: TE
authors.lastname: Jones
authors.affiliation: Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, 600 Moye Blvd. East Carolina University, Greenville, NC 27834, USA; The Harriet and John Wooten Laboratory for Alzheimer's and Neurodegenerative Diseases Research, East Carolina University, 600 Moye Blvd. East Carolina University, Greenville, NC 27834, USA. Electronic address: luq@ecu.edu.
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Physical Therapy, College of Allied Health Sciences, East Carolina University, 600 Moye Blvd. East Carolina University, Greenville, NC 27834, USA; The Harriet and John Wooten Laboratory for Alzheimer's and Neurodegenerative Diseases Research, East Carolina University, 600 Moye Blvd. East Carolina University, Greenville, NC 27834, USA. Electronic address: bareisss@ecu.edu.
authors.forename: Sonja K
authors.initials: SK
authors.lastname: Bareiss
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000097:blood / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010805:Physical Conditioning, Animal
chemical_list: D015415:Biomarkers; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018946:Chemokine CCL5
keywords: Alzheimer’s disease; Biomarkers; Chemokines; Exercise