Exacerbation of Apoptosis in the Dentate Gyrus of the Aged Rat by Dexamethasone and the Protective Role of Corticosterone

Hassan, Ali; Rosenstiel, Philipp von; Patchev, Vladimir K.; Holsboer, Florian; Almeida, O. F. X.

doi:10.1006/exnr.1996.0113

Cited by 171 publications

(126 citation statements)

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“…In line with this view, studies by Hassan et al (1996Hassan et al ( , 1999 and Almeida et al (2000) showed that corticosterone and dexamethasone given at low dosages can exert opposite effects on hippocampal cell viability. It is yet unclear whether these opposing effects are due to differences in penetration of these two corticosteroids through the blood brain barrier or whether they are due to differences in relative occupation of GR and MR.…”

Section: Functional Impairment Of Central Corticosteroid Receptors CLmentioning

confidence: 77%

The Corticosteroid Receptor Hypothesis of Depression

Holsboer

2000

Neuropsychopharmacology

1,997

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Clinical EvidenceUntil now, the serendipitous discovery of antidepressants in the 1950s has profoundly inspired hypotheses of the pathogenesis of depression. The well-known pharmacological effects of antidepressants on presynaptic uptake transporters and degradating enzymes (i.e., MAO) of serotonin and norepinephrine has focused research on causality and treatment of depression on the metabolism of functional biogenic amines and the capacity of their respective receptors to alter intracellular signaling pathways that ultimately induce changes in gene activity. Elevated circulating levels of stress hormones among depressives were recognized even before antidepressants were discovered, but these changes were seen as epiphenomena, reflecting the stressful experience of depression, although M. Bleuler (1919) already demonstrated that hormones have diverse psychotropic effects and suggested hormone treatments as potential antidepressants. A vast amount of evidence has accumulated, that reject the view that altered stress hormone secretions in depression are epiphenomenal. During the past decade, several research groups formulated a hypothesis relating aberrant stress hormone dysregulation to causality of depression and submitted that antidepressants may act through normalisation of these HPA changes (

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Section: Functional Impairment Of Central Corticosteroid Receptors CLmentioning

confidence: 77%

The Corticosteroid Receptor Hypothesis of Depression

Holsboer

2000

Neuropsychopharmacology

1,997

1,228

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“…14,23 TdT was purchased from MBI Fermentas (Heidelberg, Germany). The abovedetailed morphometric procedures were used to quantify numbers of apoptotic (TUNEL positive) as a proportion of Hoechst-stained cells.…”

Section: Detection Of Apoptosis By Tunel Histochemistrymentioning

confidence: 99%

“…To detect GR and MR mRNA transcripts in the cultures, total RNA, free from chromosomal DNA contamination, was isolated (RNAeasy kit, Qiagen, Hilden, Germany) and reverse transcribed with SUPERSCRIPTt II RNA H-reverse transcriptase (Life Technologies) using custom-synthesized oligo-dT [12][13][14][15][16][17][18] primers (MWG Biotech, Ebersberg, Germany). Published primers 24 were used and amplification conditions were denaturation for 40 s at 941C, annealing for 1 min at 621C (MR) or 401C (GR), and primer extension for 2 min at 721C; optimal amplifications of MR and GR mRNA were achieved after 35 and 25 cycles, respectively.…”

Section: Reverse-transcriptase Pcrmentioning

confidence: 99%

“…9 While most of the hippocampal shrinkage observed may be due to neuritic atrophy, including dendritic impoverishment and synaptic loss, [10][11][12] other experiments have demonstrated that GR activation activates a molecular cascade, leading to significant levels of neuronal cell death through apoptotic mechanisms. 13 Besides apoptosis of mature hippocampal neurons, 14 there is also evidence that GRs interfere with proliferation of granule neurons of the dentate gyrus. 15 MR and GR both bind cortisol/corticosterone, albeit with differing affinities: whereas GR become occupied by corticosteroid levels in the high physiological range, MR appear to be tonically active under basal levels of HPA activity, and there is evidence that activity of the two receptors is coordinated so as to maintain endocrinological and behavioral balance.…”

mentioning

confidence: 99%

“…1,16,17 We previously proposed that the relative occupation of MR and GR also contributes to maintenance of hippocampal cell numbers, since activation of MR counteract deleterious GC actions on neuronal survival. 11,13,14 Indeed, the results of earlier studies suggest that MR occupation may be essential for the survival of dentate granule neurons. [18][19][20] The interpretation of previous data showing that DEX can induce neuronal cell death in animals has been questioned on the basis that because DEX poorly penetrates the brain and produces 'chemical adrenalectomy' by suppressing pituitary ACTH secretion, the observed cell loss may reflect abolition of MR activation rather than a direct effect of GR activation.…”

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confidence: 99%

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Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation

et al. 2005

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An important question arising from previous observations in vivo is whether glucocorticoids can directly influence neuronal survival in the hippocampus. To this end, a primary postnatal hippocampal culture system containing mature neurons and expressing both glucocorticoid (GR) and mineralocorticoid (MR) receptors was developed. Results show that the GR agonist dexamethasone (DEX) targets neurons (microtubule-associated protein 2-positive cells) for death through apoptosis. GR-mediated cell death was counteracted by the MR agonist aldosterone (ALDO). Antagonism of MR with spironolactone ([7a-(acetylthio)-3-oxo-17a-pregn-4-ene-21 carbolactone] (SPIRO)) causes a dose-dependent increase in neuronal apoptosis in the absence of DEX, indicating that nanomolar levels of corticosterone present in the culture medium, which are sufficient to activate MR, can mask the apoptotic response to DEX. Indeed, both SPIRO and another MR antagonist, oxprenoate potassium ((7a,17a)-17-hydroxy-3-oxo-7-propylpregn-4-ene-21-carboxylic acid, potassium salt (RU28318)), accentuated DEX-induced apoptosis. These results demonstrate that GRs can act directly to induce hippocampal neuronal death and that demonstration of their full apoptotic potency depends on abolition of survival-promoting actions mediated by MR. Molecular Psychiatry (2005) 10, 790-798.

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Stress and Adult Neurogenesis

and

Gould

2011

The Handbook of Stress

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Exacerbation of Apoptosis in the Dentate Gyrus of the Aged Rat by Dexamethasone and the Protective Role of Corticosterone

Cited by 171 publications

References 0 publications

The Corticosteroid Receptor Hypothesis of Depression

The Corticosteroid Receptor Hypothesis of Depression

Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation

Stress and Adult Neurogenesis

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