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  • Brain Corticosteroid Receptor Balance in Health and Disease -- de Kloet et al. 19 (3): 269 -- Endocrine Reviews: Here we will highlight the determinants of brain corticosteroid receptor activity and examine the various levels at which their function may change. The molecular and cellular responses mediated by, in particular, hippocampal corticosteroid receptors will be considered in the context of HPA regulation and associated behavioral responses. The thesis is pursued that MRs are involved in maintenance of stress system activity, while GRs (in coordination with MRs) mediate steroid control of recovery from stress. Also, new findings on the MR-GR interplay are discussed that either challenge or support the original thesis. Next, we will argue that (early) life events superimposed on genotype program the stress system for the rest of one?s life and contribute to individual differences in vulnerability to stress-related psychopatholog y. Further understanding of the role of corticosteroid s in gene-environme nt interactions may help to answer a fundamental question in the endocrinology of stress and

April 22nd

  • The acute effects of corticosteroid s on cognition: integration of animal and human model studies: In this article, we review the effects of corticosteroid s on animal and human cognition and propose a theoretical framework that leads to testable predictions regarding the acute effects of corticosteroid s on cognitive function. We also discuss some methodological and experimental factors that might explain some discrepancies in data obtained from animals and humans. Furthermore, we suggest new experimental protocols for use in humans, based on animal literature, that could help resolve these discrepancies and assess more clearly the nature of the cognitive deficits induced by acute administration of corticosteroid s.
  • Stress and glucocorticoid s affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus: We found that single or repeated immobilization markedly reduced brain-derived neurotrophic factor (BDNF) mRNA levels in the dentate gyrus and hippocampus. In contrast, NT-3 mRNA levels were increased in the dentate gyrus and hippocampus in response to repeated but not acute stress. Stress did not affect the expression of neurotrophin-4 , or tyrosine receptor kinases (trkB or C). Corticosterone negative feedback may have contributed in part to the stress-induced decreases in BDNF mRNA levels, but stress still decreased BDNF in the dentate gyrus in adrenalectomiz ed rats suggesting that additional components of the stress response must also contribute to the observed changes in BDNF. However, corticosterone -mediated increases in NT-3 mRNA expression appeared to be primarily responsible for the effects of stress on NT-3.
  • Heterodimeriza tion between mineralocortic oid and glucocorticoid receptors increases the functional diversity of corticosteroid action: Ligand-activat ed steroid receptors usually regulate the expression of responsive genes by binding to common response elements on DNA as homodimers. However, recent findings indicate that mineralocortic oid and glucocorticoid receptors are able to interact by forming heterodimers. In tissues coexpressing both of these corticosteroid receptors, heterodimeriza tion between them may be a hitherto unrecognized modality for the transcriptiona l regulation of corticosteroid -responsive genes. In this review, Thorsten Trapp and Florian Holsboer discuss the potential impact of this heterodimeriza tion on corticosteriod physiology and pharmacology
  • Corticosteroid receptor mRNA expression in the brains of patients with epilepsy: We used a sensitive competitive RT-PCR assay to quantify the amounts of GR and MR mRNA in human brain tissue specimens from patients with focal epilepsies. GR and MR mRNAs were expressed at approximately the same levels in the temporal lobe, frontal lobe, and hippocampus as compared to tissues with high glucocorticoid /mineralocorti coid receptor expression (liver/kidney) . GR and MR mRNA concentrations in the temporal lobe increased markedly during childhood and reached adult levels at puberty. GR and MR mRNA expression was significantly higher in the temporal lobe and frontal lobe cortex of women than in those of men. In women, MR and GR mRNA concentrations were markedly lower in hippocampal tissue than in frontal and temporal lobe cortex tissue. In conclusion, our data demonstrate sex- and site-dependent expression of corticosteroid receptor mRNA in the human brain
  • Stress and Memory: Opposing Effects of Glucocorticoid s on Memory Consolidation and Memory Retrieval: This paper reviews recent findings from this laboratory on the acute effects of glucocorticoid s in rats on specific memory phases, i.e., memory consolidation and memory retrieval. The evidence suggests that the consequences of glucocorticoid activation on cognition depend largely on the different memory phases investigated. Posttraining activation of glucocorticoid -sensitive pathways involving glucocorticoid receptors enhances memory consolidation in a pattern highly similar to that previously described for adrenal catecholamines . Also, similar to catecholamine effects on memory consolidation, glucocorticoid influences on memory consolidation depend on noradrenergic activation of the basolateral complex of the amygdala and interactions with other brain regions. By contrast, memory retrieval processes are usually impaired with high circulating levels of glucocorticoid s or following infusions of glucocorticoid receptor agonists into the hippocampus.
  • Corticosteroid s and cognition: In this paper we review the literature on glucocorticost eroid effects on cognition and delineate specific functions that appear to be causally affected. We draw a possible connection to specific areas of brain perturbation, including the hippocampus and frontal lobe regions. The possibility that cognitive dysfunction caused by glucocorticoid s can be pharmacologica lly managed is introduced.

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