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Sex-specific fear acquisition following early life stress is linked to amygdala glutamate metabolism

ABSTRACT: Early life stress (ELS) can negatively impact health, increasing the risk of stress-related disorders like PTSD. Importantly, PTSD disproportionately affects women, highlighting the need to investigate how sex interacts with genetic risk factors (e.g., FKBP5) and trauma-related behaviors. This study uses the limited bedding and nesting (LBN) paradigm to model ELS and delve into the sex-specific consequences on fear memory formation. Employing innovative unsupervised behavioral classification, we revealed distinct behavioral patterns associated with fear acquisition and retrieval in male and female mice following ELS. Females exposed to LBN displayed heightened active fear responses, contrasting with males. Furthermore, the study examined the crucial link between behavioral regulation and cellular metabolism in key brain regions involved in fear and stress processing. Sex-specific and stress-dependent alterations were observed in purine, pyrimidine, and glutamate metabolism within the basolateral amygdala, the dorsal hippocampus, and the ventral hippocampus. These findings provide novel insights into the complex interplay between metabolic pathways, the neurobiological underpinnings of fear memory, and stress responses. Importantly, they emphasize the significance of considering sex-specific metabolic alterations when investigating stress-related disorders, opening potential avenues for the development of targeted interventions.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: PD Dr. Mathias V. Schmidt

PROVIDER: MSV000096480 | MassIVE | Wed Nov 20 23:55:00 GMT 2024

REPOSITORIES: MassIVE

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