Head trauma impairs HPA-axis functions by increased R-loop structure and shortens telomeres

Abstract

ABSTRACTTraumatic brain injury (TBI) causes inflammation, one of the main causes of cellular aging. Telomere repeat-containing RNA (TERRA) hybridizes to telomere regions, forming R-loop structures and ensuring genome stabilization. Deregulation of R-loop homeostasis leads to genomic instability linked to neurodegenerative diseases and cancer. The hypothalamus-pituitary-adrenal (HPA) axis response is critical to maintaining homeostasis after TBI. We showed that the local increase in the transcription levels of theCrhandPomcgenes, in particular, suggests a defensive response through transcriptional alteration against mild TBI despite the decreased rate in the serum in the chronic phase. Additionally, changes in the transcription levels of TERRA and correlations with hormonal deficits after repetitive mTBI head trauma were observed. Telomere shortening and increased hybridized TERRA levels, especially after repeated mTBI in the chronic phase, suggest a possible disorder of genome stabilization and loss of cellular function in tissues of the hypothalamus, pituitary, and adrenal glands.