Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses

Abstract

Although cognitive performance in humans and experimental animals can be improved by administering the omega-3 fatty acid docosahexaenoic acid (DHA), the neurochemical mechanisms underlying this effect remain uncertain. In general, nutrients or drugs that modify brain function or behavior do so by affecting synaptic transmission, usually by changing the quantities of particular neurotransmitters present within synaptic clefts or by acting directly on neurotransmitter receptors or signal-transduction molecules. We find that DHA also affects synaptic transmission in mammalian brain: Brain cells of gerbils or rats receiving this fatty acid manifest increased levels of phosphatides and of specific pre-or post-synaptic proteins. They also exhibit increased numbers of dendritic spines on postsynaptic neurons. These actions are markedly enhanced in animals that have also received the other two circulating precursors for phosphatidylcholine -uridine (which gives rise to brain UTP and CTP), and choline (which gives rise to phosphocholine). The actions of DHA are reproduced by eicosapentaenoic acid (EPA), another omega-3 compound, but not by the omega-6 fatty acid arachidonic acid (AA). Administration of circulating phosphatide precursors can also increase neurotransmitter release (acetylcholine; dopamine) and affect animal behavior. Conceivably, this treatment might have use in patients with the synaptic loss that characterizes Alzheimer's disease or other neurodegenerative diseases, or occurs after stroke or brain injury.

Oral fish oil restores striatal dopamine release after traumatic brain injury

“…In a previous study, supplementing the diet of gerbils with DHA increased hippocampal dendritic spines, as well as synaptic proteins such as PSD-95 and syntaxin-1 [10,36]. While EPA also increased synaptic protein levels, arachidonic acid (omega-6 fatty acid) did not.…”

A nutrient combination designed to enhance synapse formation and function improves outcome in experimental spinal cord injury

“…We have collected pilot data that showed an increase in synaptic markers (synaptophysin, PSD-95, synapsin 1, and syntaxin 3), rostral to the epicentre of the injury, and an improved level of myelin proteins such as MBP, in the spinal cord tissues of rats fed the high-dose FC-enriched diet for 4 weeks (data not shown). This is an important outcome that will deserve further detailed investigation, since PSD-95, syntaxin 3, and the synapsins are known regulators of neurite elongation, membrane expansion, or the growth of dendritic spines (Ferreira and Rapoport, 2002;Darios and Davletov, 2006;Cansev and Wurtman, 2007;Cansev et al, 2008). Neurite elongation and the formation of dendritic spines and synaptic membranes are dependent upon an adequate supply of circulating dietary compounds for the synthesis of new phospholipids (Wurtman et al, 2009b).…”

Serum Phospholipid Docosahexaenonic Acid Is Associated with Cognitive Functioning during Middle Adulthood

“…Both EPA and DHA also serve as precursors to eicosanoids, docosanoids, resolvins, and related compounds while also serving as ligands to a variety of nuclear receptors (34). DHA, in particular, increases cell viability via neuroprotective and antiapoptotic mechanisms (35,36) while also promoting dendritic arborization and synaptogenesis (37).…”