Alpha-Linolenic Acid Confers Neuroprotection and Improves Behavioral Deficits After Soman Exposure: Involvement of Neurogenesis Through an mTOR-Mediated Pathway

Soman, an organophosphorous (OP) compound, is a chemical warfare agent that irreversibly inhibits acetylcholinesterase in the periphery and central nervous system. Soman induces status epilepticus leading to brain damage associated with long-term cognitive and behavioral deficits. Current countermeasures are only effective when administered shortly after exposure to nerve agents and there are no therapies that protect against the long-term cognitive and behavioral impairments, which call for the search of new and efficacious therapies. Alpha linolenic acid (LIN) is an essential omega-3 polyunsaturated fatty acid (PUFA) found in green leaves, seed oil (flaxseeds), beans and walnuts. The compound can be purchased over-the-counter and has no side effects. Administration of a single dose of alpha-linolenic acid has been demonstrated to exert a potent neuroprotective effect against neuronal degeneration induced by kainic acid, transient global ischemia and organophosphates in vivo. However, the molecular mechanism(s) of LIN-induced neuroprotection administered after soman have not been delineated.