α-Methyltryptophan mitigates cognitive impairment in db/db mice: involvement of gut-brain metabolic remodeling.

ABSTRACT:

Background

Cognitive dysfunction in diabetes significantly impairs quality of life, yet effective therapies remain limited. Our previous work showed that α-methyltryptophan (α-MT), an inhibitor of the amino acid transporter SLC6A14 and indoleamine 2,3-dioxygenase 1 (IDO1), ameliorates diabetic nephropathy by modulating renal metabolism. Given its role in metabolic regulation, we hypothesized that α-MT may also protect against cognitive decline in diabetes by influencing gut-brain metabolic crosstalk.

Methods

Db/db mice were used as an in vivo model of type 2 diabetes, complemented by high-glucose-treated Caco-2 cells in vitro. Cognitive function was assessed using the Morris water maze. Gene expression related to synaptic plasticity (c-FOS, ARC, BDNF, EGR1) was measured by R

SUBMITTER: Cai A 

PROVIDER: S-EPMC12539042 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature