Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling

International Journal of Molecular Sciences

卷:21

Raffaella Molteni¹  Maria Serena Paladini¹  Giulia Corsini²  Giulia Sbrini²  Giorgio Racagni²  Francesca Calabrese²  Paola Brivio² 

[1] Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, 20133 Milan, Italy;

[2] Department of Pharmacological and Biomolecular Sciences, Università deglI Studi di Milano, 20133 Milan, Italy;

关键词: chronic stress;    restraint stress;    BDNF;    BDNF signaling;   

DOI  :  10.3390/ijms21176261

来源: DOAJ

【 摘 要 】

Depression is a recurrent disorder, with about 50% of patients experiencing relapse. Exposure to stressful events may have an adverse impact on the long-term course of the disorder and may alter the response to a subsequent stressor. Indeed, not all the systems impaired by stress may normalize during symptoms remission, facilitating the relapse to the pathology. Hence, we investigated the long-lasting effects of chronic restraint stress (CRS) and its influence on the modifications induced by the exposure to a second hit on brain-derived neurotrophic factor (BDNF) signaling in the prefrontal cortex (PFC). We exposed adult male Sprague Dawley rats to 4 weeks of CRS, we left them undisturbed for the subsequent 3 weeks, and then we exposed animals to one hour of acute restraint stress (ARS). We found that CRS influenced the release of corticosterone induced by ARS and inhibited the ability of ARS to activate mature BDNF, its receptor Tropomyosin receptor kinase B (TRKB), and their associated intracellular cascades: the TRKB-PI3K-AKT), the MEK-MAPK/ERK, and the Phospholipase C  (PLC pathways, positively modulated by ARS in non-stressed animals. These results suggest that CRS induces protracted and detrimental consequences that interfere with the ability of PFC to cope with a challenging situation.

【 授权许可】

Unknown