Long-chain polyunsaturated fatty acids modulate interleukin-1beta-induced changes in behavior, monoaminergic neurotransmitters, and brain inflammation in rats.
Recent evidence has suggested that an imbalance between membrane (n-3) and (n-6) fatty acids may contribute to the etiology of autoimmune and neurodegenerative diseases. In this study, the mechanisms by which eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and arachidonic acid (AA) modulate neurotransmitters, behavior, and brain inflammation were evaluated in rats that received central saline or interleukin-1beta (IL-1) administrations. In rats treated with saline, only the AA-enriched diet significantly increased anxiety-like behavior in the elevated plus maze, which was associated with increased corticosterone secretion. AA also increased the turnover of dopamine (DA), noradrenaline (NA), and serotonin (5-HT) in the amygdala and increased the prostaglandin (PG)E(2) level in the hippocampus. IL-1 administration slowed rat learning in the water maze and increased anxiety-like behavior, changes which were associated with increased homovanillic acid and 5-HT turnover, decreased NA in the hippocampus and amygdala, decreased DA in the frontal cortex, and decreased IL-10 in limbic brain regions. Increased corticosterone secretion following IL-1 administration was accompanied by increased NA turnover in the hippocampus (P < 0.05) and increased PGE(2) concentration (P < 0.01) in the limbic brain regions. Of the 3 diets tested, only EPA attenuated IL-1-induced behavioral changes (P < 0.05 or 0.01), which was associated with the modulation of EPA on the neuroendocrine and immune changes induced by IL-1. GLA reduced hippocampal PGE(2) concentration in rats given IL-1 (P < 0.01). AA did not counteract any of the changes induced by IL-1. These results suggest that EPA, GLA, and AA play different roles in the neuroendocrine-immune network.
Song
Cai
C
Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada C1A 4P3. cai.song@nrc.gc.ca
Manku
Mehar S
MS
Horrobin
David F
DF
D000679:Amygdala / Q000737:chemistry; D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000032:analysis / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004032:Diet; D015232:Dinoprostone / Q000032:analysis; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage; D004660:Encephalitis / Q000139:chemically induced*; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D005625:Frontal Lobe / Q000737:chemistry; D006624:Hippocampus / Q000737:chemistry; D007031:Hypothalamus / Q000737:chemistry; D007370:Interferon Type I / Q000008:administration & dosage; D016753:Interleukin-10 / Q000032:analysis; D053583:Interleukin-1beta / Q000008:administration & dosage*; D008297:Male; D018377:Neurotransmitter Agents / Q000032:analysis / Q000378:metabolism*; D000073878:Palm Oil; D010938:Plant Oils / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D017965:gamma-Linolenic Acid / Q000008:administration & dosage
D015306:Biogenic Monoamines; D005231:Fatty Acids, Unsaturated; D007370:Interferon Type I; D053583:Interleukin-1beta; D018377:Neurotransmitter Agents; D010938:Plant Oils; D011994:Recombinant Proteins; D016753:Interleukin-10; D016718:Arachidonic Acid; D000073878:Palm Oil; D017965:gamma-Linolenic Acid; D015118:Eicosapentaenoic Acid; D015232:Dinoprostone; D003345:Corticosterone