ReviewCorticosteroid receptors and neuroplasticity
Introduction
The limbic system, and in particular the hippocampus and the medial prefrontal cortex (mPFC), serves pivotal roles in cognition (Squire and Zola, 1996) as well as in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis. Accumulating evidence shows that corticosteroid modulation of hippocampal and mPFC activity and plasticity may underlie some aspects of the physiological and behavioral effects of chronic stress. A brief overview of the functional characteristics of corticosteroid receptors will be presented, and their role as key players of the stress-induced functional and structural effects will be revisited, with the intention to provide an integrative perspective on the underpinning mechanisms and their implications in clinical settings.
Section snippets
Corticosteroid receptors
Based on differing biochemical and functional characteristics, two types of corticosteroid receptors were described in the rat brain (Reul and de Kloet, 1985). The so-called Type I, or the high-affinity mineralocorticoid receptor (MR), is most densely localized in hippocampal and septal neurons, but is also present in cortical neurons. The Type II or glucocorticoid receptor (GR) is ubiquitously distributed in neurons and glial cells. Due to their pharmacological properties, MRs are activated at
Electrophysiological actions—within and from the hippocampus
The modulation of neuronal function by corticosteroids is well documented. One example is the induction of long-term potentiation (LTP) in the hippocampus which shows a specific pattern: LTP is observed when corticosteroids are kept within normal basal levels (Diamond et al., 1992), but it is impaired when corticosteroid levels are elevated (e.g. during stress) when, presumably, both GRs and MRs are occupied. Importantly, hypercorticalism is also known to facilitate long-term depression (LTD)
“Endophenotypes” and targets of intervention
Several issues remain unresolved in the field of stress research, one of the most fundamental questions being why, under seemingly similar conditions, some individuals are more vulnerable to stress-induced brain pathology. The wide spectrum of reactions to psychosocial challenges in the normal population varies between two extremes: the ability to mount a robust fight/flight response versus an apparent passive conservation/withdrawal response (Bracha, 2004, McEwen, 2004).
Individual variations
Conclusions and future perspectives
In summary, the evidence reviewed here indicates that MRs and GRs assume opposite roles in regulating synaptic plasticity, especially under stressful conditions. Besides the hippocampus, recent data demonstrate that MR and GR exert differential control over the structure of other brain regions such as the mPFC. MR activation, possibly by recruiting other players (e.g. growth factors), seems to be prerequisite for ‘positive’ neuroplastic events, whereas GR appears to be detrimental for the
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