Broad-based nutritional supplementation in 3xTg mice corrects mitochondrial function and indicates sex-specificity in response to Alzheimer's disease intervention.
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.
Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
Andrew B
AB
Wolf
B Blair
BB
Braden
Heather
H
Bimonte-Nelson
Yael
Y
Kusne
Nicole
N
Young
Elizabeth
E
Engler-Chiurazzi
Alexandra N
AN
Garcia
Douglas G
DG
Walker
Guna S D
GS
Moses
Hung
H
Tran
Frank
F
LaFerla
LihFen
L
Lue
Nancy
N
Emerson Lombardo
Jon
J
Valla
D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000178:diet therapy* / Q000523:psychology*; D000686:Amyloidosis / Q000473:pathology; D000818:Animals; D003071:Cognition / Q000502:physiology; D019587:Dietary Supplements; D003576:Electron Transport Complex IV / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019788:Fluorodeoxyglucose F18; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D028361:Mitochondrial Diseases / Q000178:diet therapy* / Q000201:enzymology; D009747:Nutritional Physiological Phenomena; D010936:Plant Extracts / Q000627:therapeutic use; D011597:Psychomotor Performance / Q000502:physiology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012727:Sex Characteristics; D016708:Synaptophysin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D010936:Plant Extracts; D019275:Radiopharmaceuticals; D016708:Synaptophysin; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18; D003576:Electron Transport Complex IV