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Session: Nutrition and the Brain: Insights from Molecular Mechanisms to Clinical Applications (Poster Theater Flash Session 7)

(PTFS07-05-24) Effects of Long-Term Dietary High Vitamin D3 Supplementation on Cognition, the Brain Transcriptome and Microbiome in Male and Female Aging F344 Rats

Sunday, June 30, 2024
12:16 PM – 12:20 PM CT
Location:  Hall F1 (The Hub) - Poster Theater
Objectives: Previously, we modeled the range of human vitamin D (VitD) levels in mid-aged male rats for 6 months from deficient to sufficient, and found that the high cholecalciferol (VitD3) diet preserved cognitive function with aging (Latimer et al., 2014). Here, we determined if the high VitD3 effects on cognition are sex-dependent, and if VitD could be acting via multiple pathways.

Methods: Twelve-month-old male and female F344 rats were fed a diet containing either standard (1,000 IU/kg of diet) or high (10,000 IU/kg) VitD3 diet for 6 months. The Morris water maze (MWM) was used to identify possible effects of VitD3 on cognition. Hippocampal gene expression, as well as an analysis of the gut microbiome (16S-rRNA) were assessed to determine possible gut-brain interactions on cognition.

Results: After 3 training days the MWM probe test showed improved memory in females, but not males, on the high VitD3 diet as indicated by reduced pathlength and latency (~70%, p=0.01) to the virtual platform. After one day of reversal training the reversal probe, conducted 2 days later, indicated VitD3 treatment significantly improved maze performance in males but not females by reducing pathlength and latency (~60%, p≤0.05). Analysis of the hippocampal transcriptome indicated that VitD3 affected gene expression to a greater extent in females than males. The microbiome analysis found 43 taxa significantly differed according to sex, and 14 taxa significantly differed according to VitD3 treatment. A Unifrac analysis of the microbiome identified significant (p≤0.01) distances between females and males, and between female control and high VitD3 groups. Female MWM probe results (combined control and Hi VitD3) were typically negatively correlated to population counts of bacteria producing short-chain fatty acids (SCFA). Both female and male groups showed no clear trends between the reversal probe and SCFA producing bacteria.

Conclusions: This study replicated our prior results showing cognitive benefits to aging male rats on a high VitD3 diet. Memory benefits also occurred in aging females but differed from males. Sexually dimorphic effects from the high VitD3 diet were observed on gene expression in the brain and on the microbiome. Our results suggest that VitD may have sexually dimorphic effects on different forms of memory and the pathways involved.

Funding Sources: NIA:AG052050 to NMP