Corticosteroid | EPFL Graph Search

Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. Some common naturally occurring steroid hormones are cortisol (C21H30O5), corticosterone (C21H30O4), cortisone (C21H28O5) and aldosterone (C21H28O5). (Note that cortisone and aldosterone are isomers.) The main corticosteroids produced by the adrenal cortex are cortisol and aldosterone. Classes

Glucocorticoids such as cortisol affect carbohydrate, fat, and protein metabolism, and have anti-inflammatory, immunosuppressive, anti-proliferative, and vasoconstrictive effects. Anti-inflammatory effects are mediated by blocking t

Genetic selection for low glucocorticoid responsiveness recapitulates PTSD-related phenotypes: a behavioral, neuroimaging and sleep-physiology study

Silvia Monari

Humans show inter-individual differences in vulnerability to develop post-traumatic stress disorder (PTSD) following exposure to trauma. Several critical biobehavioral features have been consistently described in PTSD patients, including blunted cortisol levels, smaller hippocampal size, sleep disturbances. However, because of the delay between trauma exposure and the onset of symptoms characteristic of PTSD, only a few longitudinal studies have tried to dissect whether these features constitute pre-trauma risk factors or consequences of the trauma. Enormous effort in animal and human studies has been dedicated to understanding mechanisms of conditioned fear and fear extinction, processes that are at the core of PTSD. However, the same progress has not been translated into psychiatric practice for PTSD. Deepening our understanding of the contribution of key factors to PTSD-related alterations can serve to develop effective treatments.In particular, with regard to low cortisol levels in PTSD pathophysiology, a causative role for blunted glucocorticoid responsiveness in PTSD has not been demonstrated yet.Here, we have addressed this question in lines of Wistar rats genetically-selected for their differential habituation of glucocorticoid responses to stress (LOW-, INTER-, HIGH-CORT Responder rats) and focused on fear extinction, a hallmark of PTSD symptomology, as one of the key features. As a first step, we looked whether divergent trajectories of glucocorticoid responsiveness were associated with brain volume abnormalities, prompted by the influential role of glucocorticoid in brain development. Notably, rats with low or high corticosterone responsiveness exhibit smaller hippocampi, regardless of trauma exposure, compared to rats with normative corticosterone levels. Similarly, the distribution of corticosteroid receptors in the hippocampus presented similarities between the LOW-CR and the HIGH-CR rats with higher mineralocorticoid receptors (MR) and less glucocorticoid receptors (GR). Although LOW- and HIGH-CR rats displayed a similar hippocampal profile at the structural and molecular levels, only LOW-CR male rats exhibited strong deficits in extinction consolidation compared to rats with 'normative' glucocorticoid responses (INTER-CR rats), and showed higher fear response both at few days and at several weeks after trauma exposure. We next tested the causal involvement of corticosterone in the fear extinction consolidation, and found that post-extinction corticosterone treatment markedly prevented the deficits in extinction memory and attenuated fear relapse. In addition, pharmacological inhibition of corticosterone levels during extinction memory consolidation, but not during training, in the INTER-CR rats led to extinction deficits at retrieval one day later. These results indicate that blunted corticosterone levels contribute to confer major vulnerability than having a small hippocampus, and that consolidation processes following extinction are mainly affected by low corticosterone levels.It is well known that glucocorticoids play an important role in memory consolidation processes and that sleep disturbances are a diagnostic criterion of PTSD. Therefore, we investigated in greater detail the sleep architecture in undisturbed condition and during the consolidation period of the extinction phase, which is known to be supported by sleep-dependent processes. In polysomnographic recordings, we found that rats with blunted corticos

EPFL2022

Neurobiological Mechanisms Involved in the Establishment and Maintenance of Dominance Hierarchies and its Modulation by Stress in Rats

Maria del Carmen Sandi Perez, Marjan Timmer

Stress can have a strong and long lasting effect on the establishment and maintenance of dominance hierarchies in rats. When two rats of a pair have not been stressed (non-stressed pair) before a first social encounter, they establish a dominance hierarchy, but the rank that is obtained during this first encounter is not maintained until a second encounter one week later. When one rat of the pair is stressed (stressed pair) before the first encounter, the stressed rat becomes subordinate during the first encounter and the hierarchy that is formed is long lasting and stable. In this thesis, the neurobiological mechanisms underlying the effects of stress on dominance hierarchies were studied. In the first study, we investigated the role of increasing corticosterone levels before or just after a first encounter between two rats of a pair in the establishment and the long-term maintenance of a dominance hierarchy. We show that pre-social encounter corticosterone treatment does not affect the outcome of the hierarchy during a first encounter, but induces a long-term memory for the hierarchy when the corticosterone-injected rat becomes dominant during the encounter, but not when it becomes subordinate. Post-social encounter corticosterone leads to a long-term maintenance of the hierarchy only when the subordinate rat of the pair is injected with corticosterone. This corticosterone effect implicates glucocorticoids in the consolidation of the memory for a recently established hierarchy. Next, we investigated the immediate and long-term changes in mRNA levels of receptors for oxytocin and vasopressin in medial amygdala and lateral septum. In subordinate rats of the stressed pairs, we found a downregulation in oxytocin receptor mRNA in medial amygdala at three hours after the first encounter, and a downregulation in vasopressin 1a receptor mRNA in lateral septum one week after the first encounter. We show that administration of an oxytocin antagonist in the medial amygdala of the subordinate rat immediately after a first encounter induces a long-term memory for the established hierarchy. Administration of a vasopressin 1a receptor antagonist in the lateral septum of the subordinate rat just before a second encounter mimics the effects of exposure to acute stress on the long-term establishment of a dominance hierarchy. These results suggest a role for oxytocin and vasopressin in the effects of stress on the long-term establishment of dominance hierarchies. Finally, we investigated the long-term effects of acute stress and hierarchy formation on the establishment of a second hierarchy with an unfamiliar opponent. We show that the behavior of stressed subordinate rats towards an unfamiliar opponent depends on the previous status of the opponent: when paired with a previously dominant rat they become subordinate, whereas they become dominant when paired with a previously subordinate rat. Furthermore, we show that monoamine oxidase A and androgen receptor mRNA levels are downregulated in the lateral septum of stressed subordinate rats at one week after the first encounter; i.e., at the time when we have observed their flexible social behavior against unfamiliar opponents. The monoamine oxidase A inhibitor clorgyline was injected into the lateral septum to examine whether there was a causal relationship between changes in monoamine oxidase A mRNA levels and offensive behavior towards an unfamiliar subordinate opponent. However, our results did not support this hypothesis. Taken together, we have shown that exposure to acute stress and a social encounter leads to changes in the mRNA levels of receptors for oxytocin, vasopressin and androgens and of monoamine oxidase A. These changes might underlie the effect of stress on the formation of a stable and long-lasting dominance hierarchy. Corticosterone plays a role in the long-term maintenance of the recently established hierarchy and hence it is an ideal candidate to mediate some of the observed neurobiological changes.

EPFL2011

A role for glucocorticoids in the long-term establishment of a social hierarchy

Maria del Carmen Sandi Perez, Marjan Timmer

Stress can affect the establishment and maintenance of social hierarchies. In the present study, we investigated the role of increasing corticosterone levels before or just after a first social encounter between two rats of a dyad in the establishment and the long-term maintenance of a social hierarchy. We show that pre-social encounter corticosterone treatment does not affect the outcome of the hierarchy during a first encounter, but induces a long-term memory for the hierarchy when the corticosterone-injected rat becomes dominant during the encounter, but not when it becomes subordinate. Post-social encounter corticosterone leads to a long-term maintenance of the hierarchy only when the subordinate rat of the dyad is injected with corticosterone. This corticosterone effect mimics previously reported actions of stress on the same model and, hence, implicates glucocorticoids in the consolidation of the memory for a recently established hierarchy.

Elsevier2010

Genetic selection for low glucocorticoid responsiveness recapitulates PTSD-related phenotypes: a behavioral, neuroimaging and sleep-physiology study

Silvia Monari

EPFL2022

Neurobiological Mechanisms Involved in the Establishment and Maintenance of Dominance Hierarchies and its Modulation by Stress in Rats

Maria del Carmen Sandi Perez, Marjan Timmer

EPFL2011