Broad-Based nutritional supplementation in 3xTg mice corrects mitochondrial function and indicates sex-specificity in response to Alzheimer's disease intervention

Andrew B. Wolf, Brittany Braden, Heather Bimonte-Nelson, Yael Kusne, Nicole Young, Elizabeth Engler-Chiurazzi, Alexandra N. Garcia, Douglas G. Walker, Guna S D Moses, Hung Tran, Frank Laferla, Lihfen Lue, Nancy Emerson Lombardo, Jon Valla

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Nutrition has been highlighted as a potential factor in Alzheimer's disease (AD) risk and decline and has been investigated as a therapeutic target. Broad-based combination diet therapies have the potential to simultaneously effect numerous protective and corrective processes, both directly (e.g., neuroprotection) and indirectly (e.g., improved vascular health). Here we administered either normal mouse chow with a broad-based nutritional supplement or mouse chow alone to aged male and female 3xTg mice and wildtype (WT) controls. After approximately 4 months of feeding, mice were given a battery of cognitive tasks and then injected with a radiolabeled glucose analog. Brains were assessed for differences in regional glucose uptake and mitochondrial cytochrome oxidase activity, AD pathology, and inflammatory markers. Supplementation induced behavioral changes in the 3xTg, but not WT, mice, and the mode of these changes was influenced by sex. Subsequent analyses indicated that differential response to supplementation by male and female 3xTg mice highlighted brain regional strategies for the preservation of function. Several regions involved have been shown to mediate responses to steroid hormones, indicating a mechanism for sex-based vulnerability. Thus, these findings may have broad implications for the human response to future therapeutics.

Original languageEnglish (US)
Pages (from-to)217-232
Number of pages16
JournalJournal of Alzheimer's Disease
Volume32
Issue number1
DOIs
StatePublished - 2012

Keywords

  • Biomarkers
  • cytochrome-c oxidase (Complex IV)
  • diet therapy
  • memory
  • sex
  • transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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    Wolf, A. B., Braden, B., Bimonte-Nelson, H., Kusne, Y., Young, N., Engler-Chiurazzi, E., Garcia, A. N., Walker, D. G., Moses, G. S. D., Tran, H., Laferla, F., Lue, L., Emerson Lombardo, N., & Valla, J. (2012). Broad-Based nutritional supplementation in 3xTg mice corrects mitochondrial function and indicates sex-specificity in response to Alzheimer's disease intervention. Journal of Alzheimer's Disease, 32(1), 217-232. https://doi.org/10.3233/JAD-2012-120478