title: Neuropathological responses to chronic NMDA in rats are worsened by dietary n-3 PUFA deprivation but are not ameliorated by fish oil supplementation.
abstract: BACKGROUND
  Dietary long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation may be beneficial for chronic brain illnesses, but the issue is not agreed on. We examined effects of dietary n-3 PUFA deprivation or supplementation, compared with an n-3 PUFA adequate diet (containing alpha-linolenic acid [18:3 n-3] but not docosahexaenoic acid [DHA, 22:6n-3]), on brain markers of lipid metabolism and excitotoxicity, in rats treated chronically with NMDA or saline.
  
  
  METHODS
  Male rats after weaning were maintained on one of three diets for 15 weeks. After 12 weeks, each diet group was injected i.p. daily with saline (1 ml/kg) or a subconvulsive dose of NMDA (25 mg/kg) for 3 additional weeks. Then, brain fatty acid concentrations and various markers of excitotoxicity and fatty acid metabolism were measured.
  
  
  RESULTS
  Compared to the diet-adequate group, brain DHA concentration was reduced, while n-6 docosapentaenoic acid (DPA, 22:5n-6) concentration was increased in the n-3 deficient group; arachidonic acid (AA, 20:4n-6) concentration was unchanged. These concentrations were unaffected by fish oil supplementation. Chronic NMDA increased brain cPLA2 activity in each of the three groups, but n-3 PUFA deprivation or fish oil did not change cPLA2 activity or protein compared with the adequate group. sPLA2 expression was unchanged in the three conditions, whereas iPLA2 expression was reduced by deprivation but not changed by supplementation. BDNF protein was reduced by NMDA in N-3 PUFA deficient rats, but protein levels of IL-1β, NGF, and GFAP did not differ between groups.
  
  
  CONCLUSIONS
  N-3 PUFA deprivation significantly worsened several pathological NMDA-induced changes produced in diet adequate rats, whereas n-3 PUFA supplementation did not affect NMDA induced changes. Supplementation may not be critical for this measured neuropathology once the diet has an adequate n-3 PUFA content.
authors.affiliation: Virginia Commonwealth University, School of Medicine, Richmond, Virginia, United States of America.
authors.forename: Vasken L
authors.initials: VL
authors.lastname: Keleshian
authors.affiliation: School of Earth and Space Exploration, Arizona State University, Phoenix, Arizona, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Kellom
authors.affiliation: College of Life Sciences, Sejong University, Gunja-dong, Gwangjin-Gu, Seoul, Korea.
authors.forename: Hyung-Wook
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, NIH, Bethesda, Maryland, United States of America.
authors.forename: Ameer Y
authors.initials: AY
authors.lastname: Taha
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, NIH, Bethesda, Maryland, United States of America.
authors.forename: Yewon
authors.initials: Y
authors.lastname: Cheon
authors.affiliation: Department of Anatomy & Neurobiology, School of Medicine, University of California Irvine, Irvine, California, United States of America.
authors.forename: Miki
authors.initials: M
authors.lastname: Igarashi
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, NIH, Bethesda, Maryland, United States of America.
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, NIH, Bethesda, Maryland, United States of America.
authors.forename: Jagadeesh S
authors.initials: JS
authors.lastname: Rao
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000009:adverse effects* / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects* / Q000494:pharmacology; D054513:Group IV Phospholipases A2 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D016202:N-Methylaspartate / Q000009:adverse effects* / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000378:metabolism; D051381:Rats
chemical_list: D004041:Dietary Fats; D018690:Excitatory Amino Acid Agonists; D015525:Fatty Acids, Omega-3; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D016202:N-Methylaspartate; D020932:Nerve Growth Factor; D054513:Group IV Phospholipases A2