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Abstract

The relationships between membrane fatty acid modification and neurite outgrowth and norepinephrine release were evaluated in PC12 cells. [3H]Norepinephrine release evoked by carbachol was unaffected by the modifications. Basal spontaneous release was elevated with increases in the degree of unsaturation using cells supplemented with n-3 fatty acids; a reverse correlation was observed for [3H]norepinephrine uptake. Supplementation of PC12 cells with either n-6 fatty acids or 18:1 also increased the basal release and decreased the uptake. Docosahexaenoic acid promoted and arachidonic acid suppressed neurite outgrowth induced by nerve growth factor. Choline acetyltransferase activity was slightly influenced by these fatty acids. Thus, modifications of PC12 cells with arachidonic acid and docosahexaenoic acid had a relatively small effect on the degree of differentiation but had pronounced but opposite effects on neurite elongation. Ethanolamine glycerophospholipid synthesis was elevated during differentiation induced by nerve growth factor and it was suppressed by added arachidonic acid but not by docosahexaenoic acid. Our results raise the possibility that the decreased phospholipid synthesis caused by arachidonate may lead to the suppression of neurite elongation.

Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA

“…The effects of EPA and DHA, but not DPA have been studied on neurite outgrowth and synaptogenesis in a variety of cell types and stages of development. Early studies focused on DHA, and found beneficial effects on neurite outgrowth in terms of overall length and complexity of outgrowth in rat pheochromocytoma-12 (PC-12) cells (Ikemoto et al, 1997 ), rat embryonic hippocampal primary cultures (Calderon and Kim, 2004 ) and rat embryonic cortical neurons (Cao et al, 2005 ). In addition to enhanced neurite outgrowth, DHA also promotes synaptogenesis and synaptic expression of synapsin, and glutamate receptors in rat hippocampal neurones (Cao et al, 2009 ).…”

Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression

“…At the membrane level, it can influence the function of the blood-brain barrier (22); it can alter membrane receptors such as rhodopsin (23); it can regulate the activity of membrane-bound enzymes (Na͞K-dependent ATPase) (24), ionic channels (25), and dopaminergic and serotoninergic neurotransmission (26,27), most probably by changing membrane fluidity (28); and it can alter signal transduction by means of effects on inositol phosphates, diacylglycerol, and protein kinase C (29). At the cellular level, DHA can protect neural cells from apoptotic death (30), stimulate neurite outgrowth in PC12 cells (31,32), induce synaptic growth cones during neuronal development (9,33,34), enhance synaptic functions (35), regulate nerve growth factor (36), and influence neuron size (37,38). Recent studies in Caenorhabditis elegans depleted of the delta-6 desaturase have provided pharmacological, ultrastructural, and electrophysiological evidence that the worms became depleted of synaptic vesicles and released low levels of neurotransmitter at cholinergic and serotonergic neuromuscular junctions (39).…”

Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus

“…Various mechanisms have been suggested to account for these physiological changes in the brain and retina, as reviewed recently by Kurlack and Stephenson (10), Lauritzen et al (11), and Salem et al (12). Briefly, DHA plays a crucial role in membrane order (membrane fluidity), which can influence the function of membrane receptors such as rhodopsin (13,14); regulation of membrane-bound enzymes (Na͞K-dependent ATPase) (15); dopaminergic and serotoninergic neurotransmission (16); signal transduction via effects on inositol phosphates, diacylglycerol, and protein kinase C (17); regulation of the synthesis of eicosanoids derived from arachidonic acid (AA) (10); regulation of gene expression (18)(19)(20); regulation of phosphatidylserine levels (21); protection of neural cells from apoptotic death (22,25); stimulation of neurite outgrowth in PC12 cells (23,24); selective accumulation of DHA by synaptic growth cones during neuronal development (23,24); regulation of nerve growth factor (29); and regulation of neuron size (26,27).…”