Journal
INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH
Volume 92, Issue 3-4, Pages 169-181Publisher
HOGREFE AG-HOGREFE AG SUISSE
DOI: 10.1024/0300-9831/a000624
Keywords
folate; vitamin B12; memory impairment; insulin resistance; insulin signaling
Categories
Funding
- National Research Foundation of Korea (NRF) - Ministry of Science and ICT [NRF-2019R1A2C1007203]
Ask authors/readers for more resources
Folate and vitamin B12 deficiencies impair memory function, glucose metabolism, and inflammation, and exacerbate bone mineral loss in rats with Alzheimer's disease-like dementia by modulating gut microbiota.
Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer's disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-beta infused rats, and its mechanism was explored. Rats that received an amyloid-beta(25-35) infusion into the CA1 region of the hippocampus were fed either control (2.5 mg folate plus 25 mu g V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 mu g V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 mu g V-B12/kg diet: AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 mu g V-B12/kg diet: AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt -> pGSK-3(3) and serum TNE-alpha and IL-1 beta levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available