Inhibition of excitotoxicity in cultured rat cortical neurons by a mixture of conjugated linoleic acid isomers.
Glutamate excitotoxicity, which is mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA receptors, directly contributes to the neuronal cell loss associated with both acute insults and chronic neurodegenerative disorders. Conjugated linoleic acid (CLA) is a group of dienoic derivatives of linoleic acid shown to have anticarcinogenic and antioxidative activities. To evaluate the effect of a mixture of CLA isomers (cis-9, trans-11 and cis-10, trans-12 octadecadienoic acids) on glutamate- and NMDA-induced excitotoxicity, primary cultures of rat cortical neurons were treated for 15 min with 300 microM glutamate or NMDA in the presence of various concentrations of CLA. After the exposure, cell cultures were maintained at 37 degrees C for 18 h in minimum essential medium supplemented with glucose. Neuronal injury was measured by a colorimetric cell proliferation assay, and a qualitative assessment was made by phase-contrast microscopy. CLA inhibited glutamate- and NMDA-induced neuronal cell death in a concentration-dependent fashion with the most effective dose for neuroprotection being 500 microM. These results demonstrate that a mixture of CLA isomers exhibits protective action against glutamate- and NMDA-induced excitotoxicity.
Joo
Nam E
NE
Department of Animal and Range Sciences, North Dakota State University, Fargo, ND 58105, USA.
Park
Chung S
CS
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000633:toxicity; D007536:Isomerism; D019787:Linoleic Acid / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016202:N-Methylaspartate; D019787:Linoleic Acid