CATÁLOGO DE INVESTIGACIONES | AÑO ACADÉMICO 2022-2023 25 Sex-dependent Effects of Angiotensin II Type 1 Receptor Blocker Candesartan in the Single Prolonged Stress Model PTSD is a disorder that affects fear behavior, anxiety, and hormone systems in the brain. Studies show that when angiotensin type 1 receptors (AT1R) in the brain are over-activated, it leads to anxiety-like behaviors and excessive microglia expression. The PTSD animal model, known as single-prolonged stress (SPS), also shows increased microglia overexpression and impaired fear extinction. In our study, we examined the effects of the AT1R blocker candesartan on behavior and microglia expression in key regions of the central nervous system involved in regulating the HPA axis and fear behavior. To test this, male and female animals were exposed to SPS and given oral dosages of candesartan. Female animals showed impaired fear extinction after one week of SPS exposure, and candesartan didn’t help reverse it. Male animals exposed to SPS showed more anxiety, but this was improved with candesartan treatment. SPS increased Iba1 microglia and AT1R cellular expression in male animals’ HYPO region, but not in females. AT1R inhibition reversed this effect. Candesartan reduces anxiety in male animals after SPS exposure by inhibiting AT1R in the HYPO region. Ortiz-Nazario, E., Denton-Ortiz, C. M., Soto-Escobar, L. D. M., Mateo-Mayol, Z., Colon-Romero, M., Hernandez-Lopez, A., & Porter, J. T. (2023). Sex-dependent effects of angiotensin II type 1 receptor blocker on molecular and behavioral changes induced by single prolonged stress. Behavioural Brain Research, 454(114639). https://doi.org/10.1016/j.bbr.2023.114639 emily ortiz nazario maestría en ciencias con especialidad en neurociencias integradas y aplicadas en neurobiología carla m. denton-ortiz, lawry d m. soto-escobar, maría colón romero y anixa hernández lópez department of basic sciences, ponce research institute, ponce health sciences university, pontifical catholic university of puerto rico mentor: dr. james porter (phsu) y dra. zaira mateo (pucpr) angiotensin ii type 1 receptor anxiety-like microglia paraventricular region sex-dependent: traumatic stress
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