Vulnerability to Depression: From Brain Neuroplasticity to Identification of Biomarkers

Blugeot, Aurélie; Rivat, Cyril; Bouvier, Elodie; Molet, Jenny; Mouchard, Amandine; Zeau, Brigitte; Bernard, Christophe; Benoliel, J.J.; Becker, C.

doi:10.1523/jneurosci.1309-11.2011

Cited by 159 publications

(154 citation statements)

References 50 publications

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“…Previous studies have identified subpopulations in rodent models that are resilient to the effects of stress (Kabbaj, 2004;Bergstrom et al, 2007;Krishnan et al, 2007;Sandi et al, 2008;Feder et al, 2009;Schmidt et al, 2010;Wood et al, 2010;Blugeot et al, 2011;Stiller et al, 2011;Taliaz et al, 2011;Castro et al, 2012). An understanding of the factors that lead to stress-induced affective behaviors, and factors that protect against these effects, can lead to the development of new approaches to diminish stress-induced depression and anxiety.…”

Section: Introductionmentioning

confidence: 99%

Distinct Effects of Repeated Restraint Stress on Basolateral Amygdala Neuronal Membrane Properties in Resilient Adolescent and Adult Rats

Hetzel

Rosenkranz

2014

Neuropsychopharmacol

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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.

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Section: Introductionmentioning

confidence: 99%

Distinct Effects of Repeated Restraint Stress on Basolateral Amygdala Neuronal Membrane Properties in Resilient Adolescent and Adult Rats

Hetzel

Rosenkranz

2014

Neuropsychopharmacol

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“…In the first part of this study, we, therefore, determined the long-term effect on respiratory rate 10 and 30 days after social defeat, a chronic emotional stress that induces an anxiety-like state (6,36,37). We also tested the involvement of the DMH and 5-HT 3 NTS receptors in this effect.…”

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confidence: 99%

Long-lasting bradypnea induced by repeated social defeat

Brouillard

Carrive

Camus

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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peated social defeat in the rat induces long-lasting cardiovascular changes associated with anxiety. In this study, we investigated the effects of repeated social defeat on breathing. Respiratory rate was extracted from the respiratory sinus arrhythmia (RSA) peak frequency of the ECG in rats subjected to social defeat for 4 consecutive days. Respiratory rate was recorded under anesthesia 6 days (Dϩ10) or 26 days (Dϩ30) after social defeat. At Dϩ10, defeated (D) rats spent less time in the open arms of the elevated plus maze test, had heavier adrenal glands, and displayed bradypnea, unlike nondefeated animals. At Dϩ30, all signs of anxiety had disappeared. However, one-half of the rats still displayed bradypnea (D L rats, for low respiratory rate indicated by a lower RSA frequency), whereas those with higher respiratory rate (D H rats) had recovered. Acute blockade of the dorsomedial hypothalamus (DMH) or nucleus tractus solitarii (NTS) 5-HT 3 receptors reversed bradypnea in all D rats at Dϩ10 and in DL rats at Dϩ30. Respiratory rate was also recorded in conscious animals implanted with radiotelemetric ECG probes. DH rats recovered between Dϩ10 and Dϩ18, whereas DL rats remained bradypneic until Dϩ30. In conclusion, social stress induces sustained chronic bradypnea mediated by DMH neurons and NTS 5-HT3 receptors. These changes are associated with an anxiety-like state that persists until Dϩ10, followed by recovery. However, bradypnea may persist in one-half of the population up until Dϩ30, despite apparent recovery of the anxiety-like state.anxiety; breathing; serotonin; social defeat; telemetric recording BREATHING AND ANXIETY ARE intimately related (44). For example, respiratory distress and asphyxia are associated with dreadful feelings, and fear and anxiety can have profound effects on breathing. Clinical studies have shown that panic disorder, characterized by acute and unexpected anxiety attacks and substantial anxiety over the possibility of experiencing further attacks, is associated with symptoms including palpitations, shortness of breath, sweating, and hyperventilation (1). In addition, high levels of anxiety-related behavior in rats are associated with elevation of the resting respiratory rate (9). The respiratory rate also decreases during certain specific responses to stress, for instance during freezing behavior in the rat, when it is associated with ultrasonic vocalizations (19). However, much less is known about the long-term effects of emotional stress on breathing. In adult rats, intense neonatal emotional stress, such as maternal separation, can lead to a decrease in breathing rate during non-rapid-eye-movement sleep (24). A lower respiratory rate was also observed in anesthetized Flinder-Sensitive rats, a well-validated animal model of depression (33). However, respiratory rate does not appear to be altered in patients with major depression, although cardiovascular changes are observed (4). Clearly, more work needs to be done to understand the long-term effects of emotional stress on breathin...

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“…To address the impact of allostatic load in adults, the authors of the reviewed study previously published that exposure to social defeat stress increases allostatic load in a subset of adult animals, making them vulnerable to subsequent chronic mild stress (CMS) and the development of depression-like behaviors (2). The vulnerable population was identified to have low serum levels of brain-derived neurotrophic factor (BDNF) and increased circulating levels of corticosterone.…”

Section: Primed For Problems: Stress Confers Vulnerability To Epilepsmentioning

confidence: 99%

Primed for Problems: Stress Confers Vulnerability to Epilepsy and Associated Comorbidities

Maguire¹

2015

Epilepsy Curr

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CommentaryAllostasis is defined as the process by which the body responds to stressors in order to regain homeostasis, which involves proper functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Allostatic load refers to the pathophysiological consequences of dealing with excessive, prolonged, or unresolved stress and is also thought to involve abnormalities in the functioning of the HPA axis (for a review, see [1]). There has been a great deal of speculation regarding the role of allostatic load in disease, and numerous correlational studies have attempted to investigate the pathological implications of allostatic load. However, as the authors state in the highlighted manuscript, "causality remains to be determined. "Through a series of studies, this group attempts to directly link allostatic load to pathophysiological outcomes. They previously demonstrated that social stress induces an allostatic load and vulnerability for depression in a subset of rats when faced with a subsequent, novel stressor (2). The authors suggest a "double-hit scenario" where the initial social defeat stressor (first hit) sensitizes a subset of animals, making them vulnerable to additional stressors (second hit). In the currently highlighted manuscript, Becker et al. extend these findings to investigate the pathophysiological implications of allostatic load acquired by exposure to a social defeat stress on epilepsy and associated comorbidities. This study, which is the basis of this Commentary, proposes that previous exposure to a stressor, which itself is insufficient to induce depression-like behavior, can alter epileptogenesis and predispose a subset of animals for associated comorbidities, including depression-like behaviors and cognitive impairments.Stress has been implicated in epilepsy given that the majority of patients report that stress either triggers or worsens their seizures (3). Consistent with a role of stress in epilepsy, the currently highlighted study demonstrates that in a subset of rats (~50%) previous exposure to social stress results in a reduced threshold to induce status epilepticus (SE), a shorter latency to SE, and increased seizure frequency in chronically epileptic rats (see Figure 3 in the Becker et al. article). These results alone are not surprising, given the fact that stress has been demonstrated to increase seizure susceptibility in a variety of experimental epilepsy models (3) and has recently been demonstrated to accelerate epileptogenesis (4). Further, administration of exogenous stress hormones-including corticosterone and corticotropin-releasing hormone (CRH)-have been shown to exert proconvulsant actions in numerous experimental models of epilepsy (for a review, see [5]). However, these studies focus on how acute and prolonged stress or exposure to glucocorticoids can alter neuronal excitability and seizure susceptibility with little regard to how changes in the functioning of the HPA axis may influence epilepsy.A large body of evidence suggests that early life stress can reprogram the H...

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Vulnerability to Depression: From Brain Neuroplasticity to Identification of Biomarkers

Cited by 159 publications

References 50 publications

Distinct Effects of Repeated Restraint Stress on Basolateral Amygdala Neuronal Membrane Properties in Resilient Adolescent and Adult Rats

Distinct Effects of Repeated Restraint Stress on Basolateral Amygdala Neuronal Membrane Properties in Resilient Adolescent and Adult Rats

Long-lasting bradypnea induced by repeated social defeat

Primed for Problems: Stress Confers Vulnerability to Epilepsy and Associated Comorbidities

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