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Enhancing cholinergic neurotransmission with Alpha-GPC

Background

L-Alpha glycerylphosphorylcholine (αGPC, choline alfoscerate) is a precursor in the biosynthesis of neuronal cell phospholipids and has been shown to increase the availability of acetylcholine (Ach) in nerve tissue. The proper functioning of acetylcholine neurotransmission is integral to healthy cognition. Disruptions in acetylcholine neurotransmission are associated with many memory-related or age-associated disorders and result in impairments in learning, memory, and cognitive processing. αGPC, which is an extract from purified soy lecithin, can elevate Ach levels to help the body enhance cognitive skills. αGPC enhances Ach neurotransmission by facilitating cell membrane fluidity and increasing the availability of neurotransmitter precursors.

Significant Findings

αGPC is a versatile compound in cholinergic neurons

Choline plays an important role in neurotransmitter and lipid metabolite synthesis. Adequate choline levels can be maintained with regular diet, and nerve cells uptake choline from the bloodstream. Choline in the nerve cell can be employed to produce essential lipid components or to synthesize acetylcholine directly. Choline derived lipid components, such as phosphatidylcholine, provide membrane fluidity and facilitate the structural reorganization of neurons. A decrease in the density of phospholipids can contribute to membrane rigidity, an indication of aging or unhealthy cells [1]. αGPC is a derivative of phosphatidylcholine and has been shown to positively influence membrane fluidity [2] and potentially reverse the effects of age-related damage in cholinergic neurons [3]. Furthermore, Alpha-GPC resides in the cell membrane and can also be catabolized to produce choline and increase acetylcholine neurotransmitter synthesis [2](Fig 1). The biological ability of this compound to act as both a precursor molecule and a structural component of the cell membrane allows it to play a beneficial role in cholinergic neurotransmission.

αGPC increases Ach release in important brain regions

The well-established role of the cholinergic system in cognitive processing has led researchers to evaluate the usefulness of αGPC. In a study using animal models, αGPC administration elevated Ach in the cerebral cortex, hippocampus, and striatum in a dose dependent manner [4](Fig 2). Once this elevation in Ach was confirmed, the same study examined the behavioral outcomes of αGPC supplementation. αGPC was co-administered with scopamine, a drug known to interfere with memory performance. Co-administration of αGPC reduced the memory impairing effects of the drug, supporting claims of improved memory performance.

Meta-analysis of αGPC human trials shows an effective therapy for memory loss

A review of thirteen published clinical trials, which examined over 4000 patients, has evaluated the role of αGPC as a therapy for memory and age-related challenges. After treatment periods ranging from three to six months, all trials reported significant improvements in clinical condition, especially during performance in attention and memory tasks [5]. In addition, each study reported significant improvements in related symptoms such as disorientation, irritability, lack of emotional control, and indifference to surroundings. In one particular study, Schettini el al. administered αGPC to 20 patients and compared them to a placebo control group. At the end of a three-month treatment period, the αGPC treated cohort demonstrated an increase in memory function of 15.6%, while the placebo-controlled group declined in memory performance by 8%, consistent with the degenerative nature of memory-disorders [5].

Nootropic properties of αGPC

Memory formation is dependent upon the coordination of various neurological processes, which can be separately influenced [6]. αGPC supplementation has been shown to increase the release of Ach in the hippocampus, a brain region necessary for the formation of new memories, which has a high density of cholinergic neurons [1]. Cholinergic enhancement in healthy subjects results in improved performance on working memory tasks. These improvements in memory function correlate with heightened activity in brain regions associated with memory encoding (Fig 3). Additional experiments led the researchers to conclude that cholinergic enhancement improves working memory by focusing perceptual processing on relevant stimuli [7]. Enhancing cholinergic transmission with αGPC might not only benefit those with memory challenges, but may also improve working memory in healthy adults.

Summary

Efficient neurotransmission in cholinergic neurons is crucial for normal memory performance. Degrading cholinergic neurons or depressed Ach neurotransmitter levels result in specific memory impairments and cognitive disturbances. αGPC has been shown to alleviate the symptoms in populations suffering from severe memory loss. In vivo studies show enhanced Ach neurotransmitter release in specific brain regions. This elevated release is made possible by αGPC’s versatility, since it is able to participate in Ach synthesis or provide neuronal membrane fluidity. Enhancing cholinergic neurotransmission in healthy subjects yields improvements in working memory tasks. These studies support the use of αGPC as a nootropic aimed at increasing Ach neurotransmission and improving memory function.

Reference

  1. Amenta F, Tayebati SK: Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction. Curr Med Chem 2008, 15:488-498.
  2. Aleppo G, Nicoletti F, Sortino MA, Casabona G, Scapagnini U, Canonico PL: Chronic L-alpha-glyceryl-phosphoryl-choline increases inositol phosphate formation in brain slices and neuronal cultures. Pharmacol Toxicol 1994, 74:95-100.
  3. Muccioli G, Raso GM, Ghe C, Di Carlo R: Effect of L-alpha glycerylphosphorylcholine on muscarinic receptors and membrane microviscosity of aged rat brain. Prog Neuropsychopharmacol Biol Psychiatry 1996, 20:323-339.
  4. Sigala S, Imperato A, Rizzonelli P, Casolini P, Missale C, Spano P: L-alpha-glycerylphosphorylcholine antagonizes scopolamine-induced amnesia and enhances hippocampal cholinergic transmission in the rat. Eur J Pharmacol 1992, 211:351-358.
  5. Parnetti L, Amenta F, Gallai V: Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data. Mech Aging Dev 2001, 122:2041-2055.
  6. Izquierdo I: Role of NMDA receptors in memory. Trends Pharmacol Sci 1991, 12:128-129.
  7. Furey ML, Pietrini P, Haxby JV: Cholinergic enhancement and increased selectivity of perceptual processing during working memory. Science 2000, 290:2315-2319.

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