title: Perturbed cholesterol homeostasis in aging spinal cord.
abstract: The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord function is affected by aging, however, the mechanisms involved are not well-understood. To characterize molecular mechanisms of spinal cord aging, microarray analyses of gene expression were performed on cervical spinal cords of aging rats. Of the metabolic and signaling pathways affected, cholesterol-associated pathways were the most comprehensively altered, including significant downregulation of cholesterol synthesis-related genes and upregulation of cholesterol transport and metabolism genes. Paradoxically, a significant increase in total cholesterol content was observed-likely associated with cholesterol ester accumulation. To investigate potential mechanisms for the perturbed cholesterol homeostasis, we quantified the expression of myelin and neuroinflammation-associated genes and proteins. Although there was minimal change in myelin-related expression, there was an increase in phagocytic microglial and astrogliosis markers, particularly in the white matter. Together, these results suggest that perturbed cholesterol homeostasis, possibly as a result of increased inflammatory activation in spinal cord white matter, may contribute to impaired spinal cord function with aging.
authors.affiliation: Neurobiology of Aging and Dementia Laboratory, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia; Preclinical Neurobiology Research Program, Centre for Brain and Mental Health Research, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, New South Wales, Australia.
authors.forename: Gemma M
authors.initials: GM
authors.lastname: Parkinson
authors.affiliation: Preclinical Neurobiology Research Program, Centre for Brain and Mental Health Research, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, New South Wales, Australia.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Dayas
authors.affiliation: Neurobiology of Aging and Dementia Laboratory, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia; Preclinical Neurobiology Research Program, Centre for Brain and Mental Health Research, University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, New South Wales, Australia. Electronic address: douglas.smith@newcastle.edu.au.
authors.forename: Doug W
authors.initials: DW
authors.lastname: Smith
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D015536:Down-Regulation; D015870:Gene Expression; D006706:Homeostasis / Q000502:physiology*; D007249:Inflammation / Q000235:genetics; D008297:Male; D009186:Myelin Sheath / Q000235:genetics* / Q000378:metabolism*; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation
chemical_list: D002784:Cholesterol
keywords: Aging; Cholesterol; Gene expression; Myelin; Spinal cord