TY - JOUR
T1 - Broad-Based nutritional supplementation in 3xTg mice corrects mitochondrial function and indicates sex-specificity in response to Alzheimer's disease intervention
AU - Wolf, Andrew B.
AU - Braden, Brittany
AU - Bimonte-Nelson, Heather
AU - Kusne, Yael
AU - Young, Nicole
AU - Engler-Chiurazzi, Elizabeth
AU - Garcia, Alexandra N.
AU - Walker, Douglas G.
AU - Moses, Guna S D
AU - Tran, Hung
AU - Laferla, Frank
AU - Lue, Lihfen
AU - Emerson Lombardo, Nancy
AU - Valla, Jon
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Biomarkers
KW - cytochrome-c oxidase (Complex IV)
KW - diet therapy
KW - memory
KW - sex
KW - transgenic mice
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U2 - 10.3233/JAD-2012-120478
DO - 10.3233/JAD-2012-120478
M3 - Article
C2 - 22796872
AN - SCOPUS:84867545294
SN - 1387-2877
VL - 32
SP - 217
EP - 232
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 1
ER -