Repeated systemic administration of the nutraceutical alpha-linolenic acid exerts neuroprotective efficacy, an antidepressant effect and improves cognitive performance when given after soman exposure

• Repeated intravenous administration of alpha-linolenic acid after soman exposure significantly protects against soman-induced neuropathology 10 days and 21 days after soman exposure.
• Repeated intravenous administration of alpha-linolenic acid after soman exposure significantly improves the soman-induced behavior deficits.
• For the first time, our group showed that soman induced a depressed-like state as determined by the Porsolt forced swim test.
• Repeated intravenous administration of alpha-linolenic acid after soman induced an anti-depressant-like activity in soman-exposed animals.
• The improvement in the soman-induced behavioral deficits by the repeated intravenous administration of alpha-linolenic acid after soman exposure correlated with the long-lasting reduction in neuronal degeneration in four well-established brain regions vulnerable to soman.

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 countermeasures 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.