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Early Differences in Dorsal Hippocampal Metabolite Levels in Males But Not Females in a Transgenic Rat Model of Alzheimer’s Disease

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Abstract

McGill-R-Thy1-APP rats express the human amyloid precursor protein carrying the Swedish and Indiana mutations. We examined the neurochemical content of the dorsal hippocampus in three-months-old male and female transgenic rats and healthy age- and gender-matched controls using in vivo 1H MRS in order to assess early metabolite alterations and whether these were similar for both genders. Whereas male and female controls had similar levels of all metabolites, differences were evident between male and female McGill-R-Thy1-APP rats. Compared with McGill-R-Thy1-APP females, McGill-R-Thy1-APP males had lower levels of myo-inositol and N-acetylaspartate (NAA). No differences in metabolite levels were evident when female control and McGill-R-Thy1-APP rats were compared, whereas McGill-R-Thy1-APP males had lower levels of glutamate, NAA and total choline compared with male controls. In addition to metabolite concentrations, metabolite ratios are reported as these are widely used. The results from this preliminary study demonstrate early metabolite alterations in the dorsal hippocampus of males in this rat model of Alzheimer’s disease, and imply that very early possible neurochemical markers of the disease are different for males and females.

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Acknowledgments

The authors thank Ingrid Heggland for genotyping, and Øystein Risa and Marte Thuen for technical help in setting up the 1H MRS experiments. We thank the Norwegian Health Association (Dementia) and the Department of Neuroscience DMF/NTNU for financial support.

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The authors have no disclosures or conflicts of interest.

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Correspondence to U. Sonnewald.

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Nilsen, L.H., Melø, T.M., Witter, M.P. et al. Early Differences in Dorsal Hippocampal Metabolite Levels in Males But Not Females in a Transgenic Rat Model of Alzheimer’s Disease. Neurochem Res 39, 305–312 (2014). https://doi.org/10.1007/s11064-013-1222-x

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  • DOI: https://doi.org/10.1007/s11064-013-1222-x

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