Age-Related Alterations in the Metabolic Profile in the Hippocampus of the Senescence-Accelerated Mouse Prone 8: A Spontaneous Alzheimer's Disease Mouse Model

Article type: Research Article

Authors: Wang, Hualong^a | Lian, Kaoqi^b | Han, Bing^a | Wang, Yanyong^a | Kuo, Sheng-Han^c | Geng, Yuan^d | Qiang, Jing^a | Sun, Meiyu^a | Wang, Mingwei^{a; d; *}

Affiliations: [a] Department of Neurology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China | [b] The School of Public Health, Hebei Medical University, Shijiazhuang, Hebei, PR China | [c] Department of Neurology, Columbia University, New York, NY, USA | [d] Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, Hebei, PR China

Correspondence: [*] Correspondence to: Mingwei Wang, Department of Neurology, The First Hospital of Hebei Medical University, 89, Dong-gang Road, Shijiazhuang 050031, Hebei, PR China. Tel.: +86 0311 85917005; Fax: +86 0311 85917290; E-mail: wmwsjz@163.com.

Abstract: Alzheimer's disease (AD), the most common age-dependent neurodegenerative disorder, produces a progressive decline in cognitive function. The metabolic mechanism of AD has emerged in recent years. In this study, we used multivariate analyses of gas chromatography-mass spectrometry measurements to determine that learning and retention-related metabolic profiles are altered during aging in the hippocampus of the senescence-accelerated mouse prone 8 (SAMP8). Alterations in 17 metabolites were detected in mature and aged mice compared to young mice (13 decreased and 4 increased metabolites), including metabolites related to dysfunctional lipid metabolism (significantly increased cholesterol, oleic acid, and phosphoglyceride levels), decreased amino acid (alanine, serine, glycine, aspartic acid, glutamate, and gamma-aminobutyric acid), and energy-related metabolite levels (malic acid, butanedioic acid, fumaric acid, and citric acid), and other altered metabolites (increased N-acetyl-aspartic acid and decreased pyroglutamic acid, urea, and lactic acid) in the hippocampus. All of these alterations indicated that the metabolic mechanisms of age-related cognitive impairment in SAMP8 mice were related to multiple pathways and networks. Lipid metabolism, especially cholesterol metabolism, appears to play a distinct role in the hippocampus in AD.

Keywords: Aging, Alzheimer's disease, cholesterol, gas chromatography-mass spectrometry, hippocampus, metabolic profiles

DOI: 10.3233/JAD-131463

Journal: Journal of Alzheimer's Disease, vol. 39, no. 4, pp. 841-848, 2014