A High Methionine, Low Folate and Low Vitamin B6/B12 Diet Causes Neurovascular Dysfunction and Subsequent Short‐Term Memory Loss

• DOI: 10.1096/fasebj.30.1_supplement.1016.1
• Publication Date: 2023-11-26T16:24:46Z
• Authors: Mohammed Nuru; Anuradha Kalani; Nino Muradashvili; David Lominadze; Neetu Tyagi
• Keywords: 2. Zero hunger; 3. Good health

Methionine is an amino acid found in rich quantities proteinaceous foods such as meats, fish and eggs. This essential high the average American diet due to protein consumption that far exceeds daily requirement. Besides previous studies showing a correlation between methionine osteoporosis, heart attacks pregnancy complications, more recent are links neurodegenerative disorders Alzheimer's dementia. However, mechanisms of methionine's effects not clear. Therefore, this study focused on neuronal vascular function brain. 8–10 week old C57BL6/J male mice were fed with enriched (1.2%), low folate (0.08mg/Kg), vitamin B 6 (0.01mg/Kg) 12 (10.4 μg/Kg) for period. Neuronal density their degeneration evaluated by assessing levels nuclear antigen Neuron‐specific enolase (NSE), while permeability was endothelial junction proteins Vascular Endothelial‐Cadherin (VE‐Cadherin) Claudin‐5 harvested brain tissue. Cerebrovascular assessed evaluating microvascular leakage fluorescently‐labeled albumin vivo. Cognitive determined measuring short‐term memory using Novel Object Recognition test (NORT). Western blot Immuno‐histochemical analyses neuronal‐degeneration markers revealed weekly increase damage diet. A significant (Integrated optical (IOD) NSE/GAPDH: 1.39 +/− 0.01) 4 weeks compared (IOD 0.99 +/−0.02) control animals. increased VE‐cadherin VE‐cadherin/GAPDH: 0.28 0.05) decreased 0.48 0.02) mice. NORT showed decrease (discrimination index (DI): 0.45 0.15) wild‐type group (DI: 0.89 +/−0.13). Collectively, our results suggest containing methionine, /B dysfunction, leading loss. Interestingly, precedes dysfunction. Support or Funding Information work supported part NIH grants HL107640‐NT, NS084823 P30 GM103507.