Piermartiri_2015_Neuromolecular.Med_17_251

Reference

Title : Alpha-Linolenic Acid-Induced Increase in Neurogenesis is a Key Factor in the Improvement in the Passive Avoidance Task After Soman Exposure - Piermartiri_2015_Neuromolecular.Med_17_251
Author(s) : Piermartiri TC , Pan H , Chen J , McDonough J , Grunberg N , Apland JP , Marini AM
Ref : Neuromolecular Med , 17 :251 , 2015
Abstract :

Exposure to organophosphorous (OP) nerve agents such as soman inhibits the critical enzyme acetylcholinesterase (AChE) leading to excessive acetylcholine accumulation in synapses, resulting in cholinergic crisis, status epilepticus and brain damage in survivors. The hippocampus is profoundly damaged after soman exposure leading to long-term memory deficits. We have previously shown that treatment with three sequential doses of alpha-linolenic acid, an essential omega-3 polyunsaturated fatty acid, increases brain plasticity in naive animals. However, the effects of this dosing schedule administered after a brain insult and the underlying molecular mechanisms in the hippocampus are unknown. We now show that injection of three sequential doses of alpha-linolenic acid after soman exposure increases the endogenous expression of mature BDNF, activates Akt and the mammalian target of rapamycin complex 1 (mTORC1), increases neurogenesis in the subgranular zone of the dentate gyrus, increases retention latency in the passive avoidance task and increases animal survival. In sharp contrast, while soman exposure also increases mature BDNF, this increase did not activate downstream signaling pathways or neurogenesis. Administration of the inhibitor of mTORC1, rapamycin, blocked the alpha-linolenic acid-induced neurogenesis and the enhanced retention latency but did not affect animal survival. Our results suggest that alpha-linolenic acid induces a long-lasting neurorestorative effect that involves activation of mTORC1 possibly via a BDNF-TrkB-mediated mechanism.

PubMedSearch : Piermartiri_2015_Neuromolecular.Med_17_251
PubMedID: 25920465

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Citations formats

Piermartiri TC, Pan H, Chen J, McDonough J, Grunberg N, Apland JP, Marini AM (2015)
Alpha-Linolenic Acid-Induced Increase in Neurogenesis is a Key Factor in the Improvement in the Passive Avoidance Task After Soman Exposure
Neuromolecular Med 17 :251

Piermartiri TC, Pan H, Chen J, McDonough J, Grunberg N, Apland JP, Marini AM (2015)
Neuromolecular Med 17 :251