Chronic corticosterone administration dose-dependently modulates A beta((1-42))- and NMDA-induced neurodegeneration in rat magnocellular nucleus basalis

[No Value] Abraham, T Harkany, KM Horvath, AH Veenema, B Penke, C Nyakas, PGM Luiten*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    The impact of glucocorticoids on beta-amyloid((1-42)) (A beta((1-42))) and NMDA-induced neurodegeneration was investigated in vivo. A beta((1-42)) or NMDA was injected into the cholinergic magnocellular nucleus basalis in adrenalectomized (ADX) rats, ADX rats supplemented with 25%, 100%, 2 x 100% corticosterone pellets, or sham-ADX controls. A beta((1-42))- or NMDA-induced damage of cholinergic nucleus basalis neurones was assessed by quantitative acetylcholinesterase histochemistry, Plasma concentrations of corticosterone and cholinergic fibre loss after A beta((1-42)) or NMDA injection showed a clear U-shaped dose-response relationship. ADX and subsequent loss of serum corticosterone potentiated both the A beta((1-42)) and NMDA-induced neurodegeneration. ADX + 25% corticosterone resulted in a 1.0-90 nM plasma corticosterone concentration, which significantly attenuated the A beta((1-42)) and NMDA neurotoxicity. ADX + 100% corticosterone (corticosterone concentrations of 110-270 nM) potently decreased both A beta((1-42))- and NMDA-induced neurotoxic brain damage, In contrast, high corticosterone concentrations of 310-650 nM potentiated A beta((1-42))- and NMDA-triggered neurodegeneration. In conclusion, chronic low or high corticosterone concentrations increase the vulnerability of cholinergic cells to neurotoxic insult, while slightly elevated corticosterone levels protect against neurotoxic injury. Enhanced neurotoxicity of NMDA in the presence of high concentrations of specific glucocorticoid receptor agonists suggests that the corticosterone effects are mediated by glucocorticoid receptors,

    Original languageEnglish
    Pages (from-to)486-494
    Number of pages9
    JournalJournal of Neuroendocrinology
    Volume12
    Issue number6
    Publication statusPublished - Jun-2000

    Keywords

    • corticosterone
    • neurodegeneration
    • neuroprotection
    • beta-amyloid
    • excitotoxicity
    • HIPPOCAMPAL CA1 NEURONS
    • ALZHEIMERS-DISEASE
    • CORTICAL-NEURONS
    • NERVOUS-SYSTEM
    • DENTATE GYRUS
    • BRAIN-DAMAGE
    • IN-VITRO
    • GLUCOCORTICOIDS
    • ADRENALECTOMY
    • DEGENERATION

    Cite this