Endogenous signaling by omega-3 docosahexaenoic acid-derived mediators sustains homeostatic synaptic and circuitry integrity
Open accessAbstract
The harmony and function of the complex brain circuits and synapses are sustained mainly by excitatory and inhibitory neurotransmission, neurotrophins, gene regulation, and factors, many of which are incompletely understood. A common feature of brain circuit components, such as dendrites, synaptic membranes, and other membranes of the nervous system, is that they are richly endowed in docosahexaenoic acid (DHA), the main member of the omega-3 essential fatty acid family. DHA is avidly retained and concentrated in the nervous system and known to play a role in neuroprotection, memory, and vision. Only recently has it become apparent why the surprisingly rapid increases in free (unesterified) DHA pool size take place at the onset of seizures or brain injury. This phenomenon began to be clarified by the discovery of neuroprotectin D1 (NPD1), the first-uncovered bioactive docosanoid formed from free DHA through 15-lipoxygenase-1 (15-LOX-1). NPD1 synthesis includes, as agonists, oxidative stress and neurotrophins. The evolving concept is that DHA-derived docosanoids set in motion endogenous signaling to sustain homeostatic synaptic and circuit integrity. NPD1 is anti-inflammatory, displays inflammatory resolving activities, and induces cell survival, which is in contrast to the pro-inflammatory actions of the many of omega-6 fatty acid family members. We highlight here studies relevant to the ability of DHA to sustain neuronal function and protect synapses and circuits in the context of DHA signalolipidomics. DHA signalolipidomics comprises the integration of the cellular/tissue mechanism of DHA uptake, its distribution among cellular compartments, the organization and function of membrane domains containing DHA phospholipids, and the precise cellular and molecular events revealed by the uncovering of signaling pathways regulated by docosanoids endowed with prohomeostatic and cell survival bioactivity. Therefore, this approach offers emerging targets for prevention, pharmaceutical intervention, and clinical translation involving DHA-mediated signaling.
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DHA is concentrated and avidly retained in phospholipids of synaptic and other neural membranes.
“Docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member, is concentrated and avidly retained in phospholipids of synaptic and other neural membranes [12, 13].”
From Hippocampal neuro-networks and dendritic spine perturbations in epileptogenesis are attenuated by neuroprotectin D1 (2015) · cites this paper as [13]
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- Authors
- Bazan, N. G., Musto, A. E., & Knott, E. J.
- Affiliations
- Louisiana State University (US)
- Corresponding author
- Bazan, Nicolas G.
- Venue
- Molecular Neurobiology
- Published
- 2011-09-15
- Volume
- 44
- Issue
- 2
- Pages
- 216-222
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- PMC
- PMC3180614
- OpenAlex
- W2016097851
- Cited by
- 125
- References
- 53
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 3 · 2022: 8 · 2021: 6 · 2020: 5 · 2019: 9 · 2018: 14 · 2017: 9 · 2016: 8 · 2015: 12 · 2014: 18 · 2013: 9 · 2012: 11
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Molecular Neurobiology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (EY0-05121, RR016816)
- National Eye Institute (R01EY005121)
- National Institute of Neurological Disorders and Stroke (R01NS046741)
- National Center for Research Resources (P20RR016816, RR016816)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- docosahexaenoic acid, omega-3 fatty acids, neuroprotectin D1, docosanoids, 15-lipoxygenase-1, synaptic homeostasis, neuroinflammation, neuroprotection, membrane domains, seizures, brain injury, cell survival
- MeSH terms
- Cell Survival, Docosahexaenoic Acids, Homeostasis, Humans, Nerve Net, Neurons, Seizures, Synapses, Signal Transduction, Fatty Acids, Omega-3, Apoptosis
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