Age-related alterations in the metabolic profile in the hippocampus of the senescence-accelerated mouse prone 8: a spontaneous Alzheimer's disease mouse model - PubMed (original) (raw)

Hualong Wang et al. J Alzheimers Dis. 2014.

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.

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Figures

Fig. 1

Fig. 1

Typical GC-MS total ion chromatograms from the hippocampus after chemical derivatization. The internal standard of heptadecanoic acid peak (A) and the selected maker peak of cholesterol (B) were labeled above.

Fig. 2

Fig. 2

The score plots from the PCA (A) and PLS-DA (B) analyses with the detected metabolites. Class 1 (■), Young mice group; Class 2 (●), Mature mice group; Class 3 (▲), Aged mice group. The PCA and PLS-DA score plots indicated that the samples from each group were scattered into three distinct regions (each sample represents one mouse, n = 5 in the young group; n = 6 in the mature group; n = 7 in the aged group).

Fig. 3

Fig. 3

Differences in metabolites were observed during aging in SAMP8 mice. Compared to the levels in young mice, NAA, oleic acid (Ole), and cholesterol (Cho) increased significantly in mature mice (&p < 0.05), and NAA, phosphoglyceride (P-Gly), and cholesterol increased significantly in aged mice (*p < 0.05). Compared to mature mice, in aged mice, only phosphoglyceride increased significantly (#p < 0.05). Compared to young mice, lactic acid (Lac), urea, malic acid (Mal), pyroglutamic acid (P-Glu), and aspartic acid (Asp) decreased significantly in mature mice (&p < 0.05), and in addition to these five metabolites, in aged mice, alanine (Ala), glycine (Gly), gamma-aminobutyric acid (GABA), butanedioic acid (But), fumaric acid (Fum), serine (Ser), and glutamate (Glu) decreased significantly (*p < 0.05). Compared to mature mice, the metabolites lactic acid, urea, butanedioic acid, fumaric acid, serine, pyroglutamic acid, and citric acid (Cit) decreased significantly in aged mice (#p < 0.05). The blank bars represented young mice, the shadow bars represented mature mice, and the dark bars represented aged mice. Data are presented as the mean ± SD (n = 5 in the young group; n = 6 in the mature group; n = 7 in the aged group).

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