Knockout of indoleamine 2,3-dioxygenase 1 gene expression improves depressive and anxiety-like phenotypes in a murine model of mild traumatic brain injury

Abstract

Background

Indoleamine 2,3-dioxygenase (IDO) modulates the kynurenine pathway and may influence post-mild traumatic brain injury (mTBI) outcomes. This study tested whether IDO knockout (IDO-KO) mice exhibit distinct behavioral profiles and neurotrophic factor levels after a mTBI.

Methods

Male C57BL/6 WT and IDO-KO mice (10–12 weeks) underwent weight-drop-induced mTBI or sham procedures. Anxiety- and depression-like behaviors were assessed 72 h later via elevated plus maze and forced swim tests, respectively. Neurotrophic factors BDNF, NGF, NT3 and GDNF levels were measured by ELISA in the ipsilateral and contralateral prefrontal cortex and hippocampus.

Results

WT mice exhibited increased anxiety- and depressive-like behaviors post-mTBI, whereas IDO-KO mice did not show these behaviors. In parallel, mTBI increased BDNF levels in the ipsilateral hippocampus that were more pronounced in IDO-KO compared to WT. IDO-KO mice also exhibited a different pattern of NGF and GDNF compared to WT after mTBI.

Conclusion

IDO deficiency prevented mTBI-induced anxiety- and depressive-like behaviors and altered neurotrophic factor levels regionally. These findings implicate IDO in post-mTBI behavioral and neurotrophic responses, warranting further study of kynurenine pathway metabolites and downstream signaling to clarify the mechanism underlying the role of IDO in mTBI outcomes.