title: Repeated systemic administration of the nutraceutical alpha-linolenic acid exerts neuroprotective efficacy, an antidepressant effect and improves cognitive performance when given after soman exposure.
abstract: 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 24h 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.
authors.affiliation: Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
authors.forename: Hongna
authors.initials: H
authors.lastname: Pan
authors.affiliation: Molecular and Cellular Biology Graduate School Program, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
authors.forename: Tetsade C B
authors.initials: TC
authors.lastname: Piermartiri
authors.affiliation: Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Medical and Clinical Psychology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
authors.forename: John
authors.initials: J
authors.lastname: McDonough
authors.affiliation: Department of Medical and Clinical Psychology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
authors.forename: Craig
authors.initials: C
authors.lastname: Oppel
authors.affiliation: Pharmacology Branch, Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States.
authors.forename: Wafae
authors.initials: W
authors.lastname: Driwech
authors.affiliation: Pharmacology Branch, Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States.
authors.forename: Kristin
authors.initials: K
authors.lastname: Winter
authors.affiliation: Pharmacology Branch, Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States.
authors.forename: Emylee
authors.initials: E
authors.lastname: McFarland
authors.affiliation: Pharmacology Branch, Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States.
authors.forename: Katelyn
authors.initials: K
authors.lastname: Black
authors.affiliation: Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
authors.forename: Taiza
authors.initials: T
authors.lastname: Figueiredo
authors.affiliation: Department of Medical and Clinical Psychology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
authors.forename: Neil
authors.initials: N
authors.lastname: Grunberg
authors.affiliation: Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States. Electronic address: Ann.marini@usuhs.edu.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Marini
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001362:Avoidance Learning / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003071:Cognition / Q000187:drug effects*; D019587:Dietary Supplements; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test; D012999:Soman / Q000633:toxicity*; D017962:alpha-Linolenic Acid / Q000008:administration & dosage*
chemical_list: D000928:Antidepressive Agents; D018696:Neuroprotective Agents; D017962:alpha-Linolenic Acid; D012999:Soman
keywords: Alpha-linolenic acid; Behavior; Neurodegeneration; Neuroprotection; Passive avoidance; Porsolt forced swim test; Rat; Soman