Sigma-1 Receptors and and their Effects on Mice with rmTBI

Repetitive mild traumatic brain (rmTBI) injury is common in contact sports, yet there are no specific treatments to mitigate the potential long-term detrimental effects of such injuries. Retrospective studies have observed athletes in contact sports such as American football, boxing, rugby, soccer, and martial arts have higher rates of Chronic Traumatic Encephalopathy (CTE), mood and behavior disturbance, motor and dementia-related diseases, and other neuropathological diseases. We propose that activation of S1R can mitigate detrimental behavioral and biochemical consequences of repetitive mild head injury in a mouse model. Sigma-1 receptors (S1R) are intracellular chaperone proteins that are involved in numerous cell processes. Among their diverse actions, activation of the S1R has been observed to reduce neurodegeneration in experimental models of stroke, Alzheimer's disease, Parkinson's disease and others. This wide range of effectiveness suggests that targeting S1R could also be beneficial for other neurological injuries including traumatic brain injury. In this short-term study of rmTBI in male mice, we observed only minor behavioral deficits 5 weeks after the last of 7 closed head injuries that may be mitigated by treatment with the prototypical S1R agonist PRE-084. However, PRE-084 itself had basal effects on cognition, making firm conclusions premature. Continued observation of these mice will help to determine whether there are additional long-term effects of the injury model