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Synaptic and molecular mechanisms underlying depression-like behavior in female rats following repetitive mild traumatic brain injury
Thesis

Synaptic and molecular mechanisms underlying depression-like behavior in female rats following repetitive mild traumatic brain injury

Kieran Morrisey
Master of Science (M.S.), Drexel University
Apr 2026
DOI:
https://doi.org/10.17918/00011347
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Morrisey_Kieran_2026992.27 kB
PDF Embargoed Access, Embargo ends: 31 May 2028

Abstract

Repetitive mild traumatic brain injury sustained during adolescence frequently results in chronic psychiatric complications, with female populations exhibiting a unique vulnerability to long term depressive disorders. While the clinical connection is well documented, the precise molecular mechanisms driving post trauma depression remain poorly understood. This study investigated the role of the central cholinergic system and the mammalian target of rapamycin signaling pathway in the development of trauma induced depressive behaviors within the nucleus accumbens. Adolescent female rats were subjected to three consecutive mild traumatic brain injuries along the midline. Five weeks post injury, subjects were treated with systemic scopolamine, rapamycin, or vehicle controls, and evaluated for depressive phenotypes utilizing the forced swim test and the sucrose splash test. Tissue from the nucleus accumbens was subsequently analyzed via western blotting to quantify the phosphorylation of key synaptic proteins. Injured subjects exhibited increases in immobility in the Forced Swim Test. The systemic administration of scopolamine successfully mitigated this depressive-like behavior. However, protein analysis of the nucleus accumbens demonstrated a potential downregulation of phosphorylated mTOR, AKT, and S6 Ribosomal proteins in the injured subjects treated with scopolamine. Furthermore, rapamycin demonstrated a mitigation of these changes. These results demonstrate that while systemic muscarinic antagonism holds translational potential for treating post-TBI depression, its therapeutic efficacy in repetitive mild traumatic brain injury models is mediated through unexpected mechanisms that may not include the mTOR pathway.

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