Key Findings:
This research is very novel as it attempts to delineate the effects of ALA on depression-like symptoms induced by soman in animals which is a toxic chemical substance and nerve agent which imapocts the the nervous system. The symptoms of mice treated with this toxin is similar to veterans exposed to nerve agents; people exposed to sarin and intentional or accidental exposure to OP pesticides. ALA increases membrane fluidity which can normalize membrane function in undamaged and damaged cells. In rats, ALA500 (α-linolenic acid, 500 nmol/kg) or vehicle was administered at 30 min, 3 days and 7 days after soman. ALA500 significantly reduced the soman-induced animal mortality 21 days after soman exposure. Significantly improved motor performance on the rotarod was found due to ALA. Depressive behavior using as version of the Porsolt forced swim test, which evaluate antidepressant efficacy. Rats exposed to soman spent significantly more time immobile compared to saline/vehicle and saline/ALA500-treated groups of animals. The mechanisms by which ALA may reduce the effects of soman are described in the study.
ABSTRACT:
α-Linolenic acid (ALA) is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP) nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE) that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders. (Authors Abstract)