Protection of cortical neurons from excitotoxicity by conjugated linoleic acid.
Conjugated linoleic acid (CLA) is an isomeric mixture of 18-carbon polyunsaturated fatty acids with conjugated double bonds derived from linoleic acid. CLA is sourced nutritionally from dairy products and ruminant animal meat and is associated with beneficial heath effects in several disorders, including cancer, atherosclerosis, diabetes, obesity, and inflammation. We investigated the potential for CLA to protect neurons from death in stroke simulated by exposing cultured mouse embryonic cortical neurons to glutamate. CLA (10 30 μM) significantly protected neuronal survival in response to glutamate (3 μM) excitotoxicity when given concurrently with glutamate. CLA (30 μM) also reduced neuron death when given up to 5 h after glutamate exposure (73.1 ± 13.3% protection, p < 0.01), suggesting potential utility as a post-injury therapeutic tool. The cis-9, trans-11 CLA isomer, which comprises about 40% of the commercial CLA mixture used, was identified as the active neuroprotective species. The other major species, trans-10, cis-12 CLA (40%) was without significant neuroprotective effect. CLA significantly increased neuronal Bcl-2 levels when given with glutamate and attenuated glutamate-induced dissipation of mitochondrial membrane potential, suggesting a stabilizing influence on mitochondrial function. These results show that CLA is capable of strong neuroprotective effects in glutamate excitotoxicity at concentrations likely achieved by consumption of CLA as a dietary supplement.
Hunt
Waylon T
WT
Department of Pharmacology and Therapeutics, University of Manitoba, Division of Neurodegenerative Disorders, St. Boniface Hospital Research Center, Winnipeg, Manitoba, Canada.
Kamboj
Amit
A
Anderson
Hope D
HD
Anderson
Christopher M
CM
D000818:Animals; D001562:Benzimidazoles; D015153:Blotting, Western; D002232:Carbocyanines; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000633:toxicity; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors
D001562:Benzimidazoles; D002232:Carbocyanines; D018690:Excitatory Amino Acid Agonists; D005456:Fluorescent Dyes; D044243:Linoleic Acids, Conjugated; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D018698:Glutamic Acid