Choline exposure reduces potentiation of N-methyl-d-aspartate toxicity by corticosterone in the developing hippocampus

Patrick J. Mulholland, Rachel L. Self, Barton R. Harris, John M. Littleton, Mark A. Prendergast

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Exposure to high levels of glucocorticoids (GCs) may adversely affect neuronal viability, particularly in the developing hippocampus, via increased function or sensitivity of N-methyl-d-aspartate (NMDA)-type glutamate receptors. Conversely, choline supplementation in the developing brain may reduce the severity of subsequent insult. The present studies aimed to examine the extent to which short-term exposure to high concentrations of corticosterone would produce neuronal injury mediated by NMDA receptor activity. These studies also assessed the ability of choline to prevent this form of injury via interactions with nicotinic acetylcholine receptors (nAChRs) expressing the α7 subunit. Organotypic hippocampal slice cultures derived from neonatal rat were pre-treated for 72 h with corticosterone (100 nM) alone or with choline (0.1-10 mM), prior to a brief (1 h) NMDA exposure (5 μM). NMDA exposure produced significant cellular damage, reflected as increased fluorescence of the non-vital marker propidium iodide, in the CA1 region. While exposure to corticosterone alone did not produce damage, pre-treatment of cultures with corticosterone markedly exacerbated NMDA-induced toxicity. Pre-treatment with choline (0.1-10 mM) alone or in combination with corticosterone markedly reduced subsequent NMDA toxicity, effects blocked by co-exposure to methyllycaconitine (100 nM), an antagonist active at nAChRs expressing the α7 subunit. These data suggest that even short-term exposure to high concentrations of GCs may adversely affect neuronal viability and that choline supplementation protects the brain from NMDA receptor-mediated damage, including that associated with hypercortisolemia.

Original languageEnglish
Pages (from-to)203-211
Number of pages9
JournalDevelopmental Brain Research
Issue number2
StatePublished - Nov 25 2004


  • Cortisol
  • Excitotoxicity
  • Glucocorticoids
  • Hippocampus
  • Neuroprotection

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology


Dive into the research topics of 'Choline exposure reduces potentiation of N-methyl-d-aspartate toxicity by corticosterone in the developing hippocampus'. Together they form a unique fingerprint.

Cite this