Vitamin D Combined with Resveratrol Prevents Cognitive Decline in SAMP8 Mice.
Vitamin D (VD) and resveratrol (RSV) are two nutritional molecules that have reported neuroprotective effects, and findings from cellular models suggest that resveratrol could potentiate vitamin D's effects. The senescence-accelerated mouse-prone 8 (SAMP8) is a useful model of Alzheimer's disease (AD)-related memory impairment.



We aimed to explore how the combination of vitamin D with resveratrol would affect memory impairments shown by SAMP8 mice, as well as the potential mechanisms.



SAMP8 mice and their control senescence-accelerated mouse resistant 1 (SAMR1) mice (10 weeks old) were divided into 5 groups, i.e. SAMR1 group, SAMP8 group, SAMP8 mice supplemented with VD group, SAMP8 mice supplemented with RSV group and SAMP8 mice supplemented with both VD and RSV group. At the end of the intervention, Morris water maze (MWM) test was used to assess cognitive function. Hippocampus and parietal cortex were dissected for further analysis.



The combination of VD and RSV significantly increased time spent in target quadrant and the number of crossing via MWM test. In hippocampus, the combined intervention significantly reduced soluble Aβ42 level and BACE1 protein expression. In cortex, the combined treatment significantly reduced phosphorylation of tau at serine404 and p-p53, as well as enhanced p-CREB protein expression. The combination also significantly reduced GFAP and p-NFκB p65 in both hippocampus and cortex.



The combined intervention might exert greater neuroprotective effects in SAMP8 mice, this might be associated with the fact that the combined intervention could positively affect amyloidogenic pathways, neuroinflammation, tau phosphorylation and probably apoptosis markers.
Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, China.
Jinbo
J
Cheng
Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, China.
Yehua
Y
Rui
Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, China.
Liqiang
L
Qin
School of Radiation Medicine and Protection, Soochow University, Suzhou, China.
Jiaying
J
Xu
Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, China.
Shufen
S
Han
Jiangsu Bio-Engineering Research Centre of Selenium, Suzhou, China.
Linxi
L
Yuan
Jiangsu Bio-Engineering Research Centre of Selenium, Suzhou, China.
Xuebin
X
Yin
Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Renai Road 199, Dushuhu Higher Education Town, Suzhou, China.
Zhongxiao
Z
Wan
D000375:Aging / Q000187:drug effects*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use*; D014807:Vitamin D / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use*; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D013267:Stilbenes; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D014807:Vitamin D; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase; D053829:Amyloid Precursor Protein Secretases; D002401:Cathepsin B; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D000077185:Resveratrol
Alzheimer's disease; Vitamin D; amyloid β; cognitive function; endoplasmic reticulum stress; neuroinflammation; resveratrol; tau phosphorylation