Author(s):
Roque, Susana ; Mesquita, Ana Raquel Marcelino ; Palha, Joana Almeida ; Sousa, Nuno ; Neves, Margarida Correia
Date: 2014
Persistent ID: http://hdl.handle.net/1822/32855
Origin: RepositóriUM - Universidade do Minho
Project/scholarship:
info:eu-repo/grantAgreement/FCT/5876-PPCDTI/116612/PT
;
info:eu-repo/grantAgreement/FCT/5876-PPCDTI/105180/PT
;
Subject(s): Maternal separation; Depressive-like behavior; CD8+ T cells; T cell CD4/CD8 ratio; Corticosterone; Anxious-like behavior; Science & Technology
Description
Maternal separation (MS), an early life stressful event, has been demonstrated to trigger neuropsychiatric disorders later in life, in particular depression. Experiments using rodents subjected to MS protocols have been very informative for the establishment of this association. However, the mechanism by which MS leads to neuropsychiatric disorders is far from being understood. This is probably associated with the multifactorial nature of depression but also with the fact that different research MS protocols have been used (that vary on temporal windows and time of exposure to MS). In the present study, MS was induced in rats in two developmental periods: for 6h per day for 14 days between postnatal days 2-15 (MS2-15) and 7-20 (MS7-20). These two periods were defined to differ essentially on the almost complete (MS2-15) or partial (MS7-20) overlap with the stress hypo-responsive period. Behavioral, immunological, and endocrine parameters, frequently associated with depressive-like behavior, were analyzed in adulthood. Irrespectively from the temporal window, both MS exposure periods led to increased sera corticosterone levels. However, only MS2-15 animals displayed depressive and anxious-like behaviors. Moreover, MS2-15 was also the only group presenting alterations in the immune system, displaying decreased percentage of CD8(+) T cells, increased spleen T cell CD4/CD8 ratio, and thymocytes with increased resistance to dexamethasone-induced cell death. A linear regression model performed to predict depressive-like behavior showed that both corticosterone levels and T cell CD4/CD8 ratio explained 37% of the variance observed in depressive-like behavior. Overall, these findings highlight the existence of "critical periods" for early life stressful events to exert programing effects on both central and peripheral systems, which are of relevance for distinct patterns of susceptibility to emotional disorders later in life.
We acknowledge the Portuguese Foundation for Science and Technology (FCT) for providing a fellowship to S. Roque (SFRH/BPD/72710/2010). This work was also supported by FCT grants (co-financed by COMPETE funds) PTDC/SAU-NEU/105180/2008 and PTDC/PSI-PCO/116612/2010 and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER).
