• Caiti-Erin Talty, Susan Murphy, and Pamela VandeVord.
• Graduate Program in Translational Biology, Medicine & Health, Virginia Tech, 325 Stanger St, Blacksburg, VA 24061, USA.
• Neuroscience. 2024 Nov 12; 560: 198210198-210.

AbstractMild traumatic brain injury (mTBI) is known to result in chronic somatic, cognitive, and emotional symptoms. Depression is commonly reported among individuals suffering from persistent concussion symptoms; however, the underlying mechanisms are not understood. The glutamatergic system has recently been linked with mTBI and depression due to reports of similar changes in expression of glutamatergic proteins. Using a closed-head controlled cortical impact (cCCI) model in adult male rats (n = 8/group), this study investigated the emergence of self-care deficits and changes in social interaction behaviors at four, eight and twelve weeks post-injury. Western blotting was used to assess associated changes in expression of glutamate transporters and N-methyl-D-aspartate (NMDA) receptor subunits at twelve weeks. Splash test results revealed deficits in self-care behaviors beginning at eight weeks, which continued through twelve weeks in the injury group. Injured animals also exhibited decreased preference for social novelty at four weeks and loss of desire for social interaction as a whole by twelve weeks. GluN1 was increased in injured animals compared to shams in the frontal cortex and amygdala, while decreased GLT-1 was observed in the hippocampus. Linear regression was performed to evaluate relationships between behavioral and molecular variables; the results suggested that injury affects these relationships in a region-dependent manner. Together, these results suggest that the development of chronic depression-like behavior was associated with changes in glutamatergic protein expression. Deeper investigations into how injury influences glutamatergic synaptic protein expression are needed, as this has the potential to affect circuit-level neurotransmission that drives depression-like behavior following mTBI.Published by Elsevier Inc.

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