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Volume 21
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10.3390/ijms21176261
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Article

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

by
Paola Brivio
1,
Giulia Sbrini
1,
Giulia Corsini
1,
Maria Serena Paladini
2,
Giorgio Racagni
1,
Raffaella Molteni
2 and
Francesca Calabrese
1,*
1
Department of Pharmacological and Biomolecular Sciences, Università deglI Studi di Milano, 20133 Milan, Italy
2
Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, 20133 Milan, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6261; https://doi.org/10.3390/ijms21176261
Submission received: 3 August 2020 / Revised: 25 August 2020 / Accepted: 26 August 2020 / Published: 29 August 2020
(This article belongs to the Section Molecular Biology)
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Abstract

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 γ (PLCγ) 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.
Keywords: chronic stress; restraint stress; BDNF; BDNF signaling chronic stress; restraint stress; BDNF; BDNF signaling
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MDPI and ACS Style

Brivio, P.; Sbrini, G.; Corsini, G.; Paladini, M.S.; Racagni, G.; Molteni, R.; Calabrese, F. Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling. Int. J. Mol. Sci. 2020, 21, 6261. https://doi.org/10.3390/ijms21176261

AMA Style

Brivio P, Sbrini G, Corsini G, Paladini MS, Racagni G, Molteni R, Calabrese F. Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling. International Journal of Molecular Sciences. 2020; 21(17):6261. https://doi.org/10.3390/ijms21176261

Chicago/Turabian Style

Brivio, Paola, Giulia Sbrini, Giulia Corsini, Maria Serena Paladini, Giorgio Racagni, Raffaella Molteni, and Francesca Calabrese. 2020. "Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling" International Journal of Molecular Sciences 21, no. 17: 6261. https://doi.org/10.3390/ijms21176261

APA Style

Brivio, P., Sbrini, G., Corsini, G., Paladini, M. S., Racagni, G., Molteni, R., & Calabrese, F. (2020). Chronic Restraint Stress Inhibits the Response to a Second Hit in Adult Male Rats: A Role for BDNF Signaling. International Journal of Molecular Sciences, 21(17), 6261. https://doi.org/10.3390/ijms21176261

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