Citation

Cominski TP, Stiritz V, Beck KD. FASEB J. 2022; 36(Suppl 1): R6196.

Copyright

(Copyright © 2022, Federation of American Societies for Experimental Biology)

DOI

10.1096/fasebj.2022.36.S1.R6196

PMID

35554362

Abstract

Traumatic brain injury (TBI) is a risk factor for suicide. Approximately 1.7 million TBIs occur each year and new TBI cases in the U.S. military have more than doubled in the last 5 years. The majority of military TBIs are mild in severity and can lead to chronic symptoms including, impulsivity, emotional instability, and impaired inhibition. Impulsivity is one of the most frequent behavioral changes seen following mTBI and involves poor response inhibition and/or poor decision making. Also, impulsivity is a key risk factor for suicide. The serotonergic system is an important modulator of impulsivity and, thus, a molecular target for understanding the behavioral changes in impulsivity that occur following mTBI. One major source of serotonin in the brain is the raphe nuclei in the pons. The serotonergic neurons in the raphe nuclei project to the prefrontal cortex, frontal cortex and hippocampus and are involved in many cognitive processes related to impulsivity and suicidality. In addition, both animal and human research indicates that the brainstem is affected in mTBI, particularly, in the lateral fluid percussion model utilized in this study. This provides additional support for the notion that mTBI may lead to dysfunction of the serotonin producing raphe nuclei located in the brain stem. In this study, changes in serotonergic gene expression in the raphe nuclei and target regions including the prefrontal cortex, frontal cortex and hippocampus were assessed using qRT-PCR. Rats sustained a single mTBI induced using the lateral fluid percussion model and were sacrificed three months following injury. Brains were extracted, flash frozen, sectioned at 300um and tissue for the raphe nuclei and target regions was collected using a 1.5 mm tissue punch. RNA was extracted from the tissue punches, reverse transcribed into cDNA and qRT-PCR was performed. The hypothesis states that mTBI leads to altered expression of serotonin related genes in the raphe nuclei and/or raphe nuclei target regions including the prefrontal cortex, frontal cortex, and hippocampus.

RESULTS show altered expression levels of tryptophan hydroxylase and serotonin transporter genes in both the medial raphe and dorsal raphe nuclei in mTBI rats compared to SHAM control rats. Changes in expression levels of the 5HT1A and 5HT2A receptor genes were also seen in the frontal cortex, prefrontal cortex, and ventral hippocampus. The current study serves to provide evidence for a link between TBI and altered serotonin levels to better understand the molecular mechanisms underlying impulsivity and suicidality in humans following TBI.

Language: en