Vitamin D Combined with Resveratrol Prevents Cognitive Decline in SAMP8 Mice.
BACKGROUND
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.


OBJECTIVE
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.


METHOD
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.


RESULTS
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.


CONCLUSION
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.
['Cheng|Jinbo|J|', 'Rui|Yehua|Y|', 'Qin|Liqiang|L|', 'Xu|Jiaying|J|', 'Han|Shufen|S|', 'Yuan|Linxi|L|', 'Yin|Xuebin|X|', 'Wan|Zhongxiao|Z|']
D000375:Aging D053829:Amyloid Precursor Protein Secretases D016229:Amyloid beta-Peptides D016564:Amyloid beta-Protein Precursor D000818:Animals D000975:Antioxidants D016282:Aspartic Acid Endopeptidases D001921:Brain D002401:Cathepsin B D003071:Cognition D003072:Cognition Disorders D004195:Disease Models, Animal D004359:Drug Therapy, Combination D038362:Glycogen Synthase Kinase 3 D020287:In Situ Nick-End Labeling D051379:Mice D009419:Nerve Tissue Proteins D010446:Peptide Fragments D000077185:Resveratrol D015398:Signal Transduction D013267:Stilbenes D014807:Vitamin D D016875:tau Proteins
Vitamin D resveratrol Alzheimer's disease cognitive function neuroinflammation tau phosphorylation amyloid β endoplasmic reticulum stress