Nashaly Irizarry-Méndez B.S, Yesenia Rivera-Escobales M.Sc, Yelitza Acosta-Pierantoni B.S, Anixa Hernandez, Maria Colon and James Porter Ph.D
Ponce Health Sciences University, Ponce Research Insititute, Ponce, Puerto Rico

INTRODUCTION: Exposure to stress can impede recovery from trauma by impairing fear extinction, a form of learning that underlie the suppression of trauma-related memories.  While research has shown that females are more susceptible to trauma than males, the sex-dependent factors contributing to this disparity remains elusive. To addres this gap in knowledge, this study aims to examine molecular changes underlying susceptibility to developing impaired fear extinction in female rodents exposed to single prolonged stress (SPS). We hypothesized that changes in the infralimbic cortex (IL) proteome after a traumatic event modulate susceptibility to developing impaired extinction.

METHODS: Adult female rats were subjected to SPS, which consist of 2hr restraint stress, 20 min of forced swim test, and ether exposure until general anesthesia. One week after the SPS, animals underwent auditory fear conditioning and extinction training. To identify protein candidates associated with susceptibility to develop impaired extinction, we compared the IL proteome profiles of female rats with poor extinction to those with good extinction.

RESULTS: Results showed that similar to people exposed to traumatic events, only a subpopulation of female rats exposed to SPS show impaired extinction. Females with poor extinction exhibited proteomic changes in the IL cortex. A similar analysis in male rats found that impaired extinction was associated with distinct IL proteome changes. This suggest that different proteins influence susceptibility to traumatic stress in female and male rats. As a future direction, we will validate proteomic findings by comparing IL protein expression via western blot in a new cohort of SPS-exposed female and male rats.

CONCLUSION: This approach will enable the identification of potential candidate proteins involved in modulating susceptibility to developing impaired fear extinction after exposure to traumatic stress in rodents which might also translate to susceptibility to develop trauma related disorders in humans.

IACUC: This research was approved by the Institutional Animal Care and Use Committee and followed the NIH guidelines for laboratory animal care (IACUC #2203000869).

ACKNOWLEDGMENTS: This project was supported by: 8G12MD007579-279 (B.R.A.I.N. CORE), R15 MH116345 ,GM082406 (NIH RISE PROGRAM), T32GM144896 (NIH G-RISE Program). Special thanks to Dr.Porter’s Lab members, RCMI-Grant NIMHD U54-007600 (Center for Collaborative Research in Health Disparities at University of Puerto Rico Medical Sciences Campus) and  R25 MH055929-26 2023 Summer Program in Neuroscience, Excellence and Success (SPINES) Fellow