Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function
Open Access
- 23 September 2009
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 111 (2), 510-521
- https://doi.org/10.1111/j.1471-4159.2009.06335.x
Abstract
Docosahexaenoic acid (DHA, 22:6n-3), the major polyunsaturated fatty acid accumulated in the brain during development, has been implicated in learning and memory, but underlying cellular mechanisms are not clearly understood. Here, we demonstrate that DHA significantly affects hippocampal neuronal development and synaptic function in developing hippocampi. In embryonic neuronal cultures, DHA supplementation uniquely promoted neurite growth, synapsin puncta formation and synaptic protein expression, particularly synapsins and glutamate receptors. In DHA-supplemented neurons, spontaneous synaptic activity was significantly increased, mostly because of enhanced glutamatergic synaptic activity. Conversely, hippocampal neurons from DHA-depleted fetuses showed inhibited neurite growth and synaptogenesis. Furthermore, n-3 fatty acid deprivation during development resulted in marked decreases of synapsins and glutamate receptor subunits in the hippocampi of 18-day-old pups with concomitant impairment of long-term potentiation, a cellular mechanism underlying learning and memory. While levels of synapsins and NMDA receptor subunit NR2A were decreased in most hippocampal regions, NR2A expression was particularly reduced in CA3, suggesting possible role of DHA in CA3-NMDA receptor-dependent learning and memory processes. The DHA-induced neurite growth, synaptogenesis, synapsin, and glutamate receptor expression, and glutamatergic synaptic function may represent important cellular aspects supporting the hippocampus-related cognitive function improved by DHA.Keywords
This publication has 54 references indexed in Scilit:
- Silent synapses and the emergence of a postsynaptic mechanism for LTPNature Reviews Neuroscience, 2008
- Endocannabinoid- and mGluR5-Dependent Short-Term Synaptic Depression in an Isolated Neuron/Bouton Preparation From the Hippocampal CA1 RegionJournal of Neurophysiology, 2008
- Role of RXR in neurite outgrowth induced by docosahexaenoic acidProstaglandins, Leukotrienes & Essential Fatty Acids, 2007
- Persistent Synaptic Activity Produces Long-Lasting Enhancement of Endocannabinoid Modulation and Alters Long-Term Synaptic PlasticityJournal of Neurophysiology, 2007
- Dietary enrichment with omega-3 polyunsaturated fatty acids reverses age-related decreases in the GluR2 and NR2B glutamate receptor subunits in rat forebrainNeurobiology of Aging, 2007
- Retinoic acid-mediated phospholipase A2 signaling in the nucleusBrain Research Reviews, 2004
- Alterations in hippocampal phospholipid profile by prenatal exposure to ethanolJournal of Neurochemistry, 2004
- Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cellsGenes & Development, 2003
- Requirement for Hippocampal CA3 NMDA Receptors in Associative Memory RecallScience, 2002
- DendritesGenes & Development, 2001