Nicotine attenuates arachidonic acid-induced neurotoxicity in cultured spinal cord neurons

Arachidonic acid release from cellular membranes due to spinal cord trauma may be one of the principal destructive events that can lead to progressive injury to spinal cord tissue. Exposure to arachidonic acid can compromise neuronal survival and viability. Because nicotine is known to be a neuropro tective agent, we propose that it can prevent arachidonic acid-induced neur otoxicity. To study this hypothesis, effects of nicotine on mitochondrial f unction, cellular energy content and apoptotic cell death were measured in cultured spinal cord neurons treated with arachidonic acid. Nicotine attenu ated arachidonic acid-induced compromised cell viability and cellular ATP l evels in spinal cord neurons. Nicotine exerted these protective effects whe n used at the concentration of 10 mu M and only after a 2-h pre-treatment b efore a co-exposure to arachidonic acid. Antagonists of nicotinic receptors , such as alpha-bungarotoxin or mecamylamine, only partially reversed these neuroprotective effects of nicotine. In addition, nicotine prevented arach idonic acid-induced activation of caspase-3 activity and apoptotic cell dea th. These results indicate that nicotine pre-treatment can exert a protecti ve effect against arachidonic acid-induced injury to spinal cord neurons. ( C) 2000 Elsevier Science B.V. All rights reserved.