Effects of age and dietary methionine restriction on cognitive and behavioural phenotypes in the rTg4510 mouse model of frontotemporal dementia
Year: 2024
Type: article
Abstract: Metabolic disorders such as diabetes and obesity are linked to neurodegenerative diseases, with evidence of lower brain glucose metabolism and insulin resistance in dementia patients. Dietary methionine restriction (MR) is a nutritional intervention that enhances insulin sensitivity and delays ageing-associated metabolic alterations, however, its impact on neurodegenerative diseases is not fully understood. Here, we examined the behavioural and metabolic phenotypes of a murine tauopathy model (rTg4510), which overexpresses human P301L mutated tau, at 6 and 12 months of age, assessing the impact of an 8-week dietary MR in the older group. While rTg4510 mice displayed progressive behavioural and motor impairments at both ages, MR led to significant benefits in the 12-month-old cohort, improving motor coordination, short-term memory, and social recognition. These effects were accompanied by increased glycolysis markers and FGF21R1 levels in the hippocampus, alongside unaltered glucose metabolism/adiposity. Overall, our results reveal the impact of MR on an FTD-mouse model, suggesting this as a potential therapeutic intervention to delay and/or improve the progression of tau-related disease. • MR diet improves habituation to a new environment in 12-month-old rTg4510 mice. • Motor coordination is ameliorated in the rTg4510 model of FTD after MR diet. • Short-term memory and social recognition are also recovered with MR. • Dietary MR increases glycolytic markers and FGFR1 in the brain of an FTD mouse model. • Increased tau and inflammatory markers seen in the brain of rTg4510 mice after MR.
Source: Neurobiology of Aging
Institution: University of Aberdeen
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,330
OpenAlex ID: W4404432243