PT  - JOURNAL ARTICLE
AU  - Calli Bennett
AU  - Jacalyn Green
AU  - Mae Ciancio
AU  - Joanna Goral
AU  - Lenore Pitstick
AU  - Matt Pytynia
AU  - Alice Meyer
AU  - Neha Kwatra
AU  - Nafisa M. Jadavji
TI  - Dietary folic acid deficiency impacts hippocampal morphology and cortical acetylcholine metabolism in adult male and female mice
AID  - 10.1101/2020.12.13.422535
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.13.422535
4099  - http://biorxiv.org/content/early/2020/12/13/2020.12.13.422535.short
4100  - http://biorxiv.org/content/early/2020/12/13/2020.12.13.422535.full
AB  - Background Recent evidence suggests that sex plays a role when there are deficiencies in one-carbon metabolism, however, the impact on brain tissue remains unknown.Objective The aim of the study was to examine the impact of sex differences and dietary folic acid deficiency on brain tissue in adult mice.Methods Male and female C57Bl/6J mice were placed on a folic acid deficient (FD) or control diet (CD) at six weeks of age. Mice were maintained on these diets for six months, after which animals were euthanized and brain tissue and serum were collected for analysis. Serum folate levels were measured. In brain tissue, hippocampal volume and morphology including cortical area 1 and 3 (CA1; CA3), and dentate gyrus thickness were measured. Apoptosis within the hippocampus was assessed using active caspase-3 immunofluorescence staining. Additionally, cortical acetylcholine metabolism was measured in brain tissue using immunofluorescence staining of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT).Results Male and female FD mice had reduced serum levels of folate. Both males and females maintained on a FD showed a decrease in the thickness of the hippocampal CA3 region. Interestingly, there was a sex difference in the levels of apoptosis within the CA1 region of the hippocampus. In cortical tissue, there were increased levels of neuronal ChAT and reduced levels of AChE in FD females and male mice.Conclusions The results indicated that FD impacts hippocampal morphology through increased apoptosis and changes acetylcholine metabolism within the cortex. The data from our study indicate a sex difference in apoptosis and differences in hippocampal morphology and choline metabolism as a result of dietary folic acid deficiency.Competing Interest StatementThe authors have declared no competing interest.