Effects of age and dietary methionine restriction on cognitive and behavioural phenotypes in the rTg4510 mouse model of frontotemporal dementia

Marina Souza Matos* (Corresponding Author), Annesha Sil, Gernot Riedel, Bettina Platt* (Corresponding Author), Mirela Delibegovic* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)24-37
Number of pages14
JournalNeurobiology of Aging
Volume146
Early online date14 Nov 2024
DOIs
Publication statusE-pub ahead of print - 14 Nov 2024

Data Availability Statement

No data availability statement.

Keywords

  • Methionine restriction
  • fibroblast growth factor 21
  • ageing
  • rTg4510
  • frontotemporal dementia
  • tauopathy

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