Research Projects

Traumatic experiences around puberty confer lifelong susceptibility to neurobehavioral deficits and psychopathologies though molecular mechanisms and reversal strategies are still obscure. Previously, we showed that peripubertal fearful experiences lead to pathological aggressive behavior in adult male mice and was associated with persistent changes in brain (Hypothalamus-Hypo and prefrontal cortex-PFC) thyroid hormone levels (TH) without affecting the circulating hormone (Rawat et al, eLife, 2022). Further, genetic ablation of Ttr, one of the key TH transporters in Hypo resulted in aggressive phenotype indicating crucial role of local TH availability in trauma induced aggressive behavior. However, mechanistic basis and reversal potential of local TH signaling in early life trauma induced aggressive behavior remained unexplored. In particular, it was not clear whether TTR alone and/or other factors regulating local TH availability are involved and thus necessitated the detailed investigation of TH transmembrane transport, intracellular deiodination, and TH receptor (TR)–mediated gene transcription. Therefore, we hypothesize that lasting impact of peripubertal stress (PPS) on brain region specific TH signaling and thereby persistent target gene expression changes results in pathological aggressive behavior. Further, activation of local TH signaling might hold potential for rescue of the behavioral abnormalities. The work will employ mouse model system and utilize cellular, molecular and behavioral approaches. The findings from this research will pave the way to a novel approach to the understanding of human behavior. The work will open up therapeutic potential of brain TH signaling in trauma induced psychiatric disorders.