Effect of Corticosterone and Adrenalectomy on NMDA‐Induced Cholinergic Cell Death in Rat Magnocellular Nucleus Basalis

Abstract

Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Abraham, N. V., Veenema, AH., Nyakas, C., Harkany, T., Bohus, BGJ., Luiten, PGM., & Ábrahám, I. (1997). Effect of corticosterone and adrenalectomy on NMDA-induced cholinergic cell death in rat magnocellular nucleus basalis. Journal of Neuroendocrinology, 9(9), 713-720. CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 22-03-2019Journal of Neuroendocrinology, 1997, Vol. 9, 713-720 Effect of Key words: corticosterone, adrenalectomy, magnocellular nucleus basalis, cortex, astrocytes, neuroprotection. AbstractThe present study demonstrates the effects of adrenalectomy and subcutaneously administered corticosterone on N-methyl-d-aspartateinduced neurodegeneration in the cholinergic magnocellular basal nucleus of the rat. NMDA was unilaterally injected into the nucleus basalis at different plasma cor ticosterone concentrations in adrenalectomized rats, in adrenalectomized animals with subcutaneously implanted cholesterol-corticosterone pellets containing 25% or 100% corticosterone, and in sham-adrenalectomized controls. The neurotoxic impact of the NMDA injection in the various experimental groups was assessed by the loss of cholinergic fibers stained with acetylcholinesterase histochemistry in the parietal neocortex. Reactive cortical astrocytes as a result of the treatments were detected by glial fibrillary acidic protein immunohistochemistr y. Measurements of the densities of astrocytes and cholinergic fibers at the injected side of the brain were carried out by image analysis. Adrenalectomy significantly potentiated the NMDA-induced neurodegeneration by 50%, while chronic administration of corticosterone significantly attenuated the NMDA-neurotoxicity in a dose-dependent manner. Compared to the ADX group, 25% cor ticosterone application reduced the NMDA damage by 37%, whereas the 100% corticosterone pellet dimished NMDA neurotoxicity by 75%. Both ADX and ADX+corticosterone implantation enhanced the NMDA-induced GFAP immunoreactivity. The increase of GFAP immunoreactivity was most pronounced in the adrenalectomized rats supplied with the 100% corticosterone pellets.The results demonstrate that corticosterone exerts a potent neuroprotective effect on NMDA-induced neurotoxicity in the magnocellular nucleus basalis. The activated astroglia suggest that astrocytes may contribute to the benefical effec...

Dexamethasone Downregulates Chemokine Receptor CXCR4 and Exerts Neuroprotection against Hypoxia/Ischemia-Induced Brain Injury in Neonatal Rats

“…The GFAP staining was carried out as previously described [32]. Briefly, thaw-mounted sections on slides were postfixed with 3% phosphate-buffered paraformaldehyde solution, followed by incubation in 0.3% H 2 O 2 and by pre-incubation with 5% normal sheep serum.…”

Action of Glucocorticoids on Survival of Nerve Cells: Promoting Neurodegeneration or Neuroprotection?1

“…In contrast, slightly elevated plasma corticosterone concentrations may exert neuroprotective effects against excitotoxic insults (25, 26). GC‐induced neuroprotection is likely to be mediated by MR action, as treatment with MR ligands (23, 53) but not with dexamethasone prevents ADX‐induced apoptosis (54, 55).…”

“…Results of both in vitro and in vivo studies indicated that GCs might trigger mechanisms that render glutamate transmission to excitotoxic dimensions in the brain. In this regard, by means of microdialysis, high GC concentrations were shown to increase the extracellular glutamate level in the hippocampus of freely moving conscious animals (25, 118, 123, 128, 129). It is noteworthy that GCs elicit an abrupt rise in the extracellular glutamate concentration in vivo , which cannot be inhibited by applying either specific antagonist for corticosteroid receptors, or by inhibitors of protein synthesis (130).…”

“…Additionally, clinical observations indicate that elevated GC concentrations and/or changes in the daily profile of GC release may be of particular relevance to the pathogenesis of psychiatric disorders, such as depression and post‐traumatic stress disorder (PTSD), as well as chronic neurodegenerative diseases like Alzheimer's disease (19–22). On the other hand, a fine‐tuned action of GCs is essential for neural development, particularly by their control of cellular differentiation, and for maintenance of neural integrity and function in adulthood as these hormones exert neuroprotective roles in adult brain in a narrow concentration‐window (23–26).…”

Transcriptional Regulation of Human Transforming Growth Factor-α in Astrocytes

“…GCs, including the synthetic DX, are known to stimulate the production of neurotrophic factors, such as basic fibroblast growth factor (bFGF) and nerve growth factor (NGF), which are vital for the survival of neurons (Mocchetti et al, 1996). Although long-lasting exposure to exceedingly high doses of corticosterone exerts deleterious effects in the brain, slightly elevated plasma corticosterone concentrations exert neuroprotection against excitotoxic insults (Abraham et al, 2000; Abraham et al, 1997). DX exerts neuroprotection in experimental setting of multiple sclerosis by reduction of iNOS expression levels in microglia (Golde et al, 2003).…”