Biochemical responses to dietary α-linolenic acid restriction proceed differently among brain regions in mice

Abstract

Previously, we noted that the dietary restriction of α-linolenic acid (ALA, n-3) for 4 weeks after weaning brought about significant decreases in the BDNF content and p38 MAPK activity in the striatum of mice, but not in the other regions of the brain, compared with an ALA-and linoleic acid (LNA, n-6)-adequate diet. In this study, we examined whether a prolonged dietary manipulation induces biochemical changes in other regions of the brain as well. Mice were fed a safflower oil (SAF) diet (ALA-restricted, LNA-adequate) or a perilla oil (PER) diet (containing adequate amounts of ALA and LNA) for 8 weeks from weaning. The docosahexaenoic acid (DHA, 22:6n-3) contents and p38 MAPK activities in the cerebral cortex, striatum and hippocampus were significantly lower in the SAF group. The BDNF contents and protein kinase C (PKC) activities in the cerebral cortex as well as in the striatum, but not in the hippocampus, were significantly lower in the SAF group. These data indicate that the biochemical changes induced by the dietary restriction of ALA have a time lag in the striatum and cortex, suggesting that the signal is transmitted through decreased p38 MAPK activity and BDNF content and ultimately decreased PKC activity.Highly unsaturated fatty acids (HUFAs, ≧ 20 carbons and ≧ 3 double bonds), mainly arachidonic acid (ARA, 20:4n-6) and docosahexaenoic acid (DHA,, are essential components of membrane lipids in the mammalian brain; they are synthesized from dietary essential fatty acids, namely, linoleic acid (LNA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3), respectively, by sequential desaturation, elongation, and/or chain shortening. Various studies have reported that the behavioral and biochemical parameters of mammalian brains are affected by long-term dietary manipulations, e.g., n-3 polyunsaturated fatty acid (PUFA) such as ALA and/or DHA, which is required for neuronal development, behavioral performance, neuroprotection, synaptic plasticity and several other functions (3,6,7,11,15,19,28,30). Long-term dietary manipulations using linoleic acid (LNA)-adequate but α-linolenic acid (ALA)-restricted diets, e.g., over the course of two generations, have been shown to modify membrane phospholipid acyl chains, learning ability and general behavior in rodents compared with diets containing adequate amounts of LNA and ALA (14,36). The nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are members of the neurotrophin family that normally plays a crucial role in neuronal development, function, survival, and plasticity. NGF is a prototype of members of the neurotrophin family that have approximately 50% amino acid sequence homologies with each other. NGF regulates neuronal survival and stimulates neural differentiation via the TrkA receptor (1,16,33). BDNF, a 27-kDa protein, regulates the survival, growth, and differentiation of new neurons during early neural development, maintaining neuro-

The review of alpha‐linolenic acid: Sources, metabolism, and pharmacology

“…ALA supplementation during pregnancy has an important effect on the offspring's nervous system development. Whether it was a short‐term or long‐term lack of ALA in weaned mice, it decreased the DHA and BDNF contents and p38 MAPK activity in the cerebral cortex and striatum (Miyazawa, Yasui, Yamada, Ohara, & Okuyama, 2010, 2011). Moreover, although postnatal ALA supplementation (75.37 nmol/mg of the diet) promoted neurogenesis in the dentate gyrus of offspring, the lack of maternal ALA supplementation during pregnancy could offset this effect (Niculescu, Lupu, & Craciunescu, 2011).…”

Botanicals as Modulators of Neuroplasticity: Focus on BDNF

“…Male mice subjected to dietary restriction of α -linolenic acid (ALA) were fed with a diet supplemented with Perilla oil (5%) for 8 weeks. ALA restriction lowered the BDNF levels in the striatum, and Perilla oil significantly increased the BDNF protein levels [ 124 , 125 ].…”

α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology

“…Interestingly, a diet restricted in α-linolenic acid reduced brain-derived neurotrophic factor (BDNF) levels in the cortex in mice [126] whereas increased intake of ALA and other polyunsaturated fatty acids increased BDNF protein levels and reduced depressive symptoms in humans and in animals [127,128,129,130,131]. Recently, epigenetic alterations in the elongation of very long-chain fatty acids protein 5 (Elovl5) of polyunsaturated fatty acids were associated depression and suicide risk [132].…”