Abstract
BackgroundDietary 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.MethodsMale 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.ResultsCompared 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.ConclusionsN-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.
Highlights
The central nervous system is highly enriched in the polyunsaturated fatty acids (PUFAs) arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3)
We reported that a chronic daily subconvulsive dose of NMDA (25 mg/kg i.p.) in adult rats decreased brain NMDA receptor subunit levels [21], and upregulated mRNA and protein levels of interleukin-1 beta (IL1b), tumor necrosis factor alpha (TNF-a), glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase in the frontal cortex [25]
At 15 weeks, mean body weight of fish oil-saline administered rats was significantly less compared to weight of the adequate group-saline administered rats (Fig. 1A)
Summary
The central nervous system is highly enriched in the polyunsaturated fatty acids (PUFAs) arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3). AA and DHA cannot be synthesized de novo by vertebrates, but must be obtained from the diet or by hepatic elongation and desaturation of their dietary essential precursors, linoleic acid (LA, 18:2n-6) and a-linolenic acid (a-LNA, 18:3n-3), respectively [1,2]. 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
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