Elsevier

Neuroscience

Volume 63, Issue 3, December 1994, Pages 691-699
Neuroscience

Arachidonic acid: Toxic and trophic effects on cultured hippocampal neurons

https://doi.org/10.1016/0306-4522(94)90515-0Get rights and content

Abstract

Arachidonic acid (20:4) is a component of membrane lipids that has been implicated as a messenger both in physiological and pathophysiological processes, including ischemic injury and synaptic plasticity. In order to clarify direct trophic or toxic effects of arachidonic acid on central neurons, primary cultures of rat hippocampal neurons were exposed to arachidonic acid under chemically-defined conditions. Arachidonic acid present in the culture medium at concentrations over5 × 10−6M showed profound toxicity, whereas at lower concentrations (10−6M) it significantly supported the survival of hippocampal neurons. These effects were not mimicked by oleic acid (18:1) or palmitic acid (16:0). The toxic action of 10−1 M arachidonic acid was markedly and significantly prevented by a lipoxygenase inhibitor nordihydroguaiaretic acid (10−6 M). AA861 and baicalein (each at 10−6 M), a selective inhibitor for 5- and 12-lipoxygenase, respectively, also showed a significant protective effect, whereas cyclooxygenase inhibitor indomethacin (10−5 M) had no effect. The toxic action was also prevented by an antioxidant α-tocopherol (10−6 M), but not by Superoxide dismutase (100 U/ml) or catalase (200 U/ml). The trophic effect of 10−6 M arachidonic acid was not suppressed by the treatments listed above. At lower concentrations (10−7−10−6 M), arachidonic acid promoted neurite elongation, which was not inhibited by nordihydroguaiaretic acid or indomethacin.

Overall, arachidonic acid has both trophic and toxic actions on cultured hippocampal neurons, part of which involves its metabolism by lipoxygenases. The mechanisms and the physiological significance of these effects are discussed.

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