Comprehensive metabolic profiling across five lifespan stages in murine hippocampus and cortex reveals sex-related variation in age-related cognitive decline.

ABSTRACT: This study employs Barnes maze behavioral assessments, untargeted liquid chromatography-mass spectrometry metabolomics, and ¹³C₆-glucose isotopic tracing to systematically investigate cognitive function and metabolic profiles in hippocampal and cortical tissues of male and female mice across five distinct age-ranges. Behavioral analyses reveal significant cognitive decline in both sexes by 16-months-of-age, with females exhibiting more severe impairment by 23-months, demonstrating a sex-related variation. ¹³C₆-glucose tracing analyses reveals that glucose is rapidly and preferentially metabolized toward the Tricarboxylic acid cycle over glycolysis and the pentose phosphate pathway (PPP), with metabolism rates increasing from juvenility to meet de

SUBMITTER: Long X 

PROVIDER: S-EPMC12905236 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature