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

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 ? (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.

SUBMITTER: Brivio P

PROVIDER: S-EPMC7503736 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Brivio Paola P Sbrini Giulia G Corsini Giulia G Paladini Maria Serena MS Racagni Giorgio G Molteni Raffaella R Calabrese Francesca F

International journal of molecular sciences 20200829 17

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 ...[more]

PMID: 32872446

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Project description:Severe and repeated stress has damaging effects on health, including initiation of depression and anxiety. Stress that occurs during development has long-lasting and particularly damaging effects on emotion. The basolateral amygdala (BLA) plays a key role in many affective behaviors, and repeated stress causes different forms of BLA hyperactivity in adolescent and adult rats. However, the mechanism is not known. Furthermore, not every individual is susceptible to the negative consequences of stress. Differences in the effects of stress on the BLA might contribute to determine whether an individual will be vulnerable or resilient to the effects of stress on emotion. The purpose of this study is to test the cellular underpinnings for age dependency of BLA hyperactivity after stress, and whether protective changes occur in resilient individuals. To test this, the effects of repeated stress on membrane excitability and other membrane properties of BLA principal neurons were compared between adult and adolescent rats, and between vulnerable and resilient rats, using in vitro whole-cell recordings. Vulnerability was defined by adrenal gland weight, and verified by body weight gain after repeated restraint stress, and fecal pellet production during repeated restraint sessions. We found that repeated stress increased the excitability of BLA neurons, but in a manner that depended on age and BLA subnucleus. Furthermore, stress resilience was associated with an opposite pattern of change, with increased slow afterhyperpolarization (AHP) potential, whereas vulnerability was associated with decreased medium AHP. The opposite outcomes in these two populations were further distinguished by differences of anxiety-like behavior in the elevated plus maze that were correlated with BLA neuronal excitability and AHP. These results demonstrate a substrate for BLA hyperactivity after repeated stress, with distinct membrane properties to target, as well as age-dependent factors that contribute to resilience to the effects of stress.

Project description:Spermiogenesis is an important physiological process of mammalian fertilization. The germ cells are susceptible to the harmful effects of either psychological or physiological stress, which could induce male infertility. Our previous studies have found that chronic psychological stress could decrease sexual motivation. However, molecular mechanisms underlying male reproductive toxicity induced by chronic stress remain elusive. Recently, autophagy is proven to be involved in regulating the survival of germ cells, which is related to apoptosis. Herein, we established a chronic psychological stress model and a chronic pain model (physiological stressor) to explore the roles of autophagy in germ cells. Thirty-two male Sprague-Dawley rats were randomly divided into four groups, including the control group, the chronic psychological stress group, the SNI-sham group, and the chronic pain stress group. After exposure to stress for 35 days, open field test and the unconditioned sexual motivation test were performed. Following the behavioral experiment, autophagy in the rat testis was detected by Western blot and immunohistochemistry. We found both chronic psychological stress and chronic pain stress reduced total travel distance, the frequency of central crossing and increased the sensitivity to mechanical pain. While chronic psychological stress, but not the chronic pain stress declined sexual motivation. Chronic psychological stress prompt the expression of LC3-II with the decreased expression of p62, indicating that chronic psychological stress induced autophagy in rat testis. However, there was no significant difference between the expression of LC3-II and p62 in male rats under chronic pain stress. Therefore, chronic psychological stress and chronic pain stress have common behavior changes, but due to its unpredictability, chronic psychological stress leads to a decline in sexual motivation in male rats and induced the autophagy in testicular tissues.

Dataset Information

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

Publications

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

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