Preconditioning with NMDA protects against toxicity of 3-nitropropionic acid or glutamate in cultured cerebellar granule neurons

Smith, A.J., Stone, T.W. and Smith, R.A. (2008) Preconditioning with NMDA protects against toxicity of 3-nitropropionic acid or glutamate in cultured cerebellar granule neurons. Neuroscience Letters, 440(3), pp. 294-298. (doi: 10.1016/j.neulet.2008.05.066)

Abstract

A brief sub-lethal ischaemic stimulus has been reported to protect against subsequent ischaemic damage in vivo, and in vitro following periods of hypoxia or oxygen-glucose deprivation (OGD). Preconditioning against neurotoxic stimuli has been linked to N-methyl-d-aspartate (NMDA) receptors, since receptor blockade prevents the protection afforded by OGD, and low doses of NMDA treatment are capable of preconditioning. The current study demonstrated that NMDA preconditioning also protects against 3-nitropropionic acid (3-NPA), a generator of both excitotoxic and oxidative damage, in addition to glutamate. Cerebellar granule neuronal (CGN) cultures prepared from 8-day neonatal Sprague-Dawley rats were maintained for 8 days prior to NMDA stimulation for 6áh. At 9 days in vitro (DIV), preconditioned and control cultures were subjected to a toxic insult (1á[mu]M-10ámM glutamate or 1á[mu]M-10ámM 3-NPA). Neuronal viability was assessed by use of a fluorescein diacetate assay. Protection was effective with 100á[mu]M NMDA preconditioning for 6áh against 1-100á[mu]M glutamate, and also against 1-500á[mu]M 3-NPA. The study demonstrates that NMDA preconditioning can be beneficial against excitotoxic treatments, even when these are potentially complicated by associated oxidative damage and metabolic compromise, as is the case for 3-NPA

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stone, Professor Trevor and Smith, Professor Robert
• Authors: Smith, A.J., Stone, T.W., and Smith, R.A.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience; College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: Neuroscience Letters
• Publisher: Elsevier
• ISSN: 0304-3940