New Jersey Department of Veterans Affairs 1I01RD001484-01A2

BCCMA: Cognitive phenotypes of emotion regulation and suicide risk in Veterans with TBI: Mechanistic Neurobehavioral Model of Emotional Reactivity

This award funds research on how traumatic brain injury affects emotional regulation and suicide risk in Veterans, using a rat model to study sex-specific brain changes and emotional responses.

Description

This VA Merit proposal is part of a BLR&D/CSR&D Collaborative Merit Award for traumatic brain injury (TBI; BCCMA) involving four proposals investigating how TBI impacts cognitive phenotypes and emotion dysregulation via multiple pathways, increasing suicide risk. The project uses a rat model of TBI to explore causal relationships between TBI, changes in brainstem noradrenergic neurons, and emotional reactivity to fear stimuli. The model involves lateral fluid percussion injury to male and female Sprague Dawley rats, causing long-lasting changes in sensory reactivity and sex-specific alterations in the locus coeruleus (LC). Emotional reactivity will be assessed through fear reactions to learned and unlearned threats, with pharmacological manipulation of noradrenergic signaling and LC activity. Sex-specific effects on LC morphology and function will be further studied, including neuroinflammation in females and orexin signaling in males. Secondary measures include autonomic responses (ECG), and tertiary measures involve fecal microbiome analysis. The research aims to elucidate sex differences in TBI-induced emotional dysregulation and its contribution to suicide risk in Veterans.

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