Efecto del estrés por aislamiento social sobre la conducta y perfil inflamatorio en ratones hembra.
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Date
2023
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Universidad de Concepción
Abstract
Diversos estudios señalan que el estrés psicosocial crónico promueve un ambiente pro inflamatorio, el cual podría explicar en parte los efectos perjudiciales sobre la fisiología del organismo. En este contexto las células T reguladoras (Treg), una subpoblación de linfocitos T CD4+CD25+Foxp3+ podrían favorecer la recuperación de la homeostasis inmune, debido a su capacidad para suprimir la función de las células T efectoras. Sin embargo, durante fenómenos inflamatorios crónicos, se observa deterioro en la función y una disminución en el número de esta población celular, lo que también se ha observado en roedores. Aun cuando se reconocen las diferencias sexuales asociadas a la fisiología del estrés, la gran mayoría de los estudios utilizan ratones macho como modelos, dejando de lado el análisis de hembras y cómo su fisiología se ve alterada. El objetivo de esta tesis es evaluar el efecto del estrés por aislamiento social en patrones conductuales y frecuencia de Linfocitos T reguladores en ratones hembra. Para ello, se sometió a hembras a un protocolo de aislamiento social por 8 semanas, tras lo cual analizamos su patrón conductual para detectar signos de ansiedad y depresión y evaluamos la presencia de cortisol y citoquinas proinflamatorias y anti-inflamatorias en bazo. Por otro lado, se analizó mediante citometría de flujo la frecuencia de las células T reguladoras y T efectoras activadas derivadas de hembras estresadas. De este modo fue posible identificar que el aislamiento social induce comportamiento depresivo en ratón hembra, pero contrario a lo que hipotetizamos, no fue posible identificar un ambiente proinflamatorio a nivel periférico en las hembras estresadas.
Various studies indicate that chronic psychosocial stress promotes a pro inflammatory environment which could partly explain the detrimental effects on the physiology of the organism. In this context, regulatory T cells (Tregs), a subpopulation of CD4+CD25+Foxp3+ T lymphocytes could favor the recovery of immune homeostasis due to their ability to suppress the function of effector T cells. However, during chronic inflammatory phenomena, impaired function and a decrease in the number of this cell population are observed which has also been observed in rodents. Even when gender differences associated with stress physiology are recognized, the vast majority of studies use male mice as models, leaving aside the analysis of females and how their physiology is altered. The objective of this thesis is to evaluate the effect of stress due to social isolation on behavioral patterns and frequency of regulatory T lymphocytes in female mice. To do this, females were subjected to a protocol of social isolation for 8 weeks, after which we analyzed their behavioral pattern to detect signs of anxiety and depression and we evaluated the presence of cortisol and proinflammatory and anti-inflammatory cytokines in the spleen. On the other hand, the frequency of regulatory T cells and effector T cells derived from stressed females was analyzed by flow cytometry. In this way, it was possible to identify that social isolation induces depressive behavior in female mice, but contrary to what we hypothesized, it was not possible to identify a proinflammatory environment at the peripheral level in stressed females.
Various studies indicate that chronic psychosocial stress promotes a pro inflammatory environment which could partly explain the detrimental effects on the physiology of the organism. In this context, regulatory T cells (Tregs), a subpopulation of CD4+CD25+Foxp3+ T lymphocytes could favor the recovery of immune homeostasis due to their ability to suppress the function of effector T cells. However, during chronic inflammatory phenomena, impaired function and a decrease in the number of this cell population are observed which has also been observed in rodents. Even when gender differences associated with stress physiology are recognized, the vast majority of studies use male mice as models, leaving aside the analysis of females and how their physiology is altered. The objective of this thesis is to evaluate the effect of stress due to social isolation on behavioral patterns and frequency of regulatory T lymphocytes in female mice. To do this, females were subjected to a protocol of social isolation for 8 weeks, after which we analyzed their behavioral pattern to detect signs of anxiety and depression and we evaluated the presence of cortisol and proinflammatory and anti-inflammatory cytokines in the spleen. On the other hand, the frequency of regulatory T cells and effector T cells derived from stressed females was analyzed by flow cytometry. In this way, it was possible to identify that social isolation induces depressive behavior in female mice, but contrary to what we hypothesized, it was not possible to identify a proinflammatory environment at the peripheral level in stressed females.
Description
Tesis presentada para optar al título de Bioquímico/a.
Keywords
Estrés, Aislamiento social, Ratones Conducta, Población celular, Hidrocortisona, Citocinas