Journal
NEUROTOXICOLOGY
Volume 51, Issue -, Pages 38-50Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.neuro.2015.09.006
Keywords
Rat; Alpha-linolenic acid; Soman; Behavior; Neuroprotection; Neurodegeneration; Passive avoidance; Porsolt forced swim test
Categories
Funding
- Defense Threat Reduction Agency-Joint Science and Technology Office, Medical ST Division [CBM.NEURO.01.10.US.012, CBM.NEURO.01.10. US.019]
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Exposure to nerve agents results in severe seizures or status epilepticus caused by the inhibition of acetylcholinesterase, a critical enzyme that breaks down acetylcholine to terminate neurotransmission. Prolonged seizures cause brain damage and can lead to long-term consequences. Current counter-measures are only modestly effective against the brain damage supporting interest in the evaluation of new and efficacious therapies. The nutraceutical alpha-linolenic acid (LIN) is an essential omega-3 polyunsaturated fatty acid that has a wide safety margin. Previous work showed that a single intravenous injection of alpha-linolenic acid (500 nmol/kg) administered before or after soman significantly protected against soman-induced brain damage when analyzed 24 h after exposure. Here, we show that administration of three intravenous injections of alpha-linolenic acid over a 7 day period after soman significantly improved motor performance on the rotarod, enhanced memory retention, exerted an anti-depressant-like activity and increased animal survival. This dosing schedule significantly reduced soman-induced neuronal degeneration in four major vulnerable brain regions up to 21 days. Taken together, alpha-linolenic acid reduces the profound behavioral deficits induced by soman possibly by decreasing neuronal cell death, and increases animal survival. Published by Elsevier Inc.
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