Phosphatidylcholine and Memory

Biomaterials. 2013 Dec;34(38):10249-57.
Functionalized liposomes loaded with siRNAs targeting ion channels in effector memory T cells as a potential therapy for autoimmunity.
Hajdu P, Chimote AA, Thompson TH, Koo Y, Yun Y, Conforti L.
University of Cincinnati, Department of Internal Medicine, Division of Nephrology and Hypertension, 231 Albert Sabin Way, Cincinnati, OH 45267-0585,USA.

ABSTRACT: Effector memory T cells (TM) play a key role in the pathology of certain autoimmune disorders. The activity of effector TM cells is under the control of Kv1.3 ion channels, which facilitate the Ca(2+) influx necessary for T cell activation and function, i.e. cytokine release and proliferation. Consequently, the knock-down of Kv1.3 expression in effector TM’s may be utilized as a therapy for the treatment of autoimmune diseases. In this study we synthesized lipid unilamellar nanoparticles (NPs) that can selectively deliver Kv1.3 siRNAs into TM cells in vitro. NPs made from a mixture of phosphatidylcholine, pegylated/biotinylated phosphoethanolamine and cholesterol were functionalized with biotinylated-CD45RO (cell surface marker of TM’s) antibodies via fluorophore-conjugated streptavidin (CD45RO-NPs). Incubation of T cells with CD45RO-NPs resulted into the selective attachment and endocytosis of the NPs into TM’s. Furthermore, the siRNA against Kv1.3, encapsulated into the CD45RO-NPs, was released into the cytosol. Consequently, the expression of Kv1.3 channels decreased significantly in TM’s, which led to a remarkable decrease in Ca(2+) influx. Our results can form the basis of an innovative therapeutic approach in autoimmunity.

Am J Psychiatry. 2013 Mar 1;170(3):290-8.
Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk.
Ross RG, Hunter SK, McCarthy L, Beuler J, Hutchison AK, Wagner BD, Leonard S, Stevens KE, Freedman R
Department of Psychiatry, Obstetrics and Gynecology, University of Colorado Denver, Aurora, USA.

ABSTRACT OBJECTIVE: Deficient cerebral inhibition is a pathophysiological brain deficit related to poor sensory gating and attention in schizophrenia and other disorders. Cerebral inhibition develops perinatally, influenced by genetic and in utero factors. Amniotic choline activates fetal α7-nicotinic acetylcholine receptors and facilitates development of cerebral inhibition. Increasing this activation may protect infants from future illness by promoting normal brain development. The authors investigated the effects of perinatal choline supplementation on the development of cerebral inhibition in human infants.
METHOD: A randomized placebo-controlled clinical trial of dietary phosphatidylcholine supplementation was conducted with 100 healthy pregnant women, starting in the second trimester. Supplementation to twice normal dietary levels for mother or newborn continued through the third postnatal month. All women received dietary advice regardless of treatment. Infants’ electrophysiological recordings of inhibition of the P50 component of the cerebral evoked response to paired sounds were analyzed. The criterion for inhibition was suppression of the amplitude of the second P50 response by at least half, compared with the first response.
RESULTS: No adverse effects of choline were observed in maternal health and delivery, birth, or infant development. At the fifth postnatal week, the P50 response was suppressed in more choline-treated infants (76%) compared with placebo-treated infants (43%) (effect size=0.7). There was no difference at the 13th week. A CHRNA7 genotype associated with schizophrenia was correlated with diminished P50 inhibition in the placebo-treated infants, but not in the choline-treated infants.
CONCLUSIONS: Neonatal developmental delay in inhibition is associated with attentional problems as the child matures. Perinatal choline activates timely development of cerebral inhibition, even in the presence of gene mutations that otherwise delay it.

Leuk Lymphoma. 2013 Mar;54(3):535-40.
Chemotherapy-related changes in central nervous system phospholipids and neurocognitive function in childhood acute lymphoblastic leukemia
Krull KR, Hockenberry MJ, Miketova P, Carey M, Moore IM.
Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN, USA. kevin. [email protected]

ABSTRACT: Long-term survivors of childhood leukemia are at risk for neurocognitive impairment, although the neurophysiological basis is not well understood. The purpose of this study was to explore associations between changes in cerebrospinal fluid (CSF) phospholipids and neurocognitive function in children undergoing chemotherapy for acute lymphoblastic leukemia. Seventy-six children were followed prospectively from diagnosis. CSF samples were collected during scheduled lumbar punctures and phospholipids were extracted. Neurocognitive evaluations were conducted annually beginning shortly after diagnosis. Concentrations of sphingomyelin (SM) increased following induction (p = 0.03) and consolidation (p = 0.04), while lysophosphatidylcholine (LPC) increased following induction (p = 0.003). Multivariable analyses demonstrated associations between post-induction SM and motor speed at 1 year (p < 0.001), 2 years (p = 0.001) and 3 years (p = 0.02) following diagnosis. Post-induction LPC was associated with verbal working memory (p = 0.007). Results indicate that early changes in phospholipids are related to neurocognitive decline and suggest a chemotherapy impact on white matter integrity.

Clin Interv Aging. 2013;8:1247-57.
Effects of krill oil containing n-3 polyunsaturated fatty acids in phospholipid form on human brain function: a randomized controlled trial in healthy elderly volunteers.
Konagai C, Yanagimoto K, Hayamizu K, Han L, Tsuji T, Koga Y.
Department of Food and Nutrition, Japan Women’s University, Bunkyo-ku, Tokyo, Japan ; Department of Neuropsychiatry, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.

ABSTRACT BACKGROUND: Krill oil, rich in n-3 (omega-3) polyunsaturated fatty acids (PUFAs) incorporated in phosphatidylcholine, has been reported to have many effects on physiological function. However, there are few studies using psychophysiological methods published that describe the effects of krill oil on brain function. We investigated the influence of ingestion of krill oil on cognitive function in elderly subjects by using near-infrared spectroscopy and electroencephalography.
METHODS: A randomized, double-blind, parallel-group comparative study design was adopted. Forty-five healthy elderly males aged 61-72 years were assigned to receive 12 weeks of treatment with: medium-chain triglycerides as placebo; krill oil, which is rich in n-3 PUFAs incorporated in phosphatidylcholine ; or sardine oil, which is abundant in n-3 PUFAs incorporated in triglycerides. Changes in oxyhemoglobin concentrations in the cerebral cortex during memory and calculation tasks were measured. The P300 component of event-related potentials was also measured during a working memory task.
RESULTS: During the working memory task, changes in oxyhemoglobin concentrations in the krill oil and sardine oil groups were significantly greater than those in the medium-chain triglyceride group at week 12. The differential value for P300 latency in the krill oil group was significantly lower than that in the medium-chain triglyceride group at week 12. With regard to the calculation task, changes in oxyhemoglobin concentrations in the krill oil group were significantly greater than those in the medium-chain triglyceride group at week 12.
CONCLUSION: This study provides evidence that n-3 PUFAs activate cognitive function in the elderly. This is especially the case with krill oil, in which the majority of n-3 PUFAs are incorporated into phosphatidylcholine, causing it to be more effective than sardine oil, in which n-3 PUFAs are present as triglycerides

Pol Merkur Lekarski. 2013 Jan;34(199):62-6.
[Milk phospholipids as nutraceutic].
Ambroziak A, Cichosz G. [Article in Polish]
Uniwersytet Warmińsko-Mazurski w Olsztynie, Katedra Mleczarstwa i Zarzadzania Jakościa.

ABSTRACT: Almost the all milk fat is closed inside fat globules possessing envelope of phospholipids, glycosphingolipids, cholesterols and proteins. Phospholipids of milk are composed of phosphatidylcholine (lecithin), phosphatidylethanolamine (kefalin), sphingomyelin, also phosphatidylinositol, phosphatidylserine and lizophosphatidylcholine (lizolecithin) and make 30% of the milk fat globule membrane. Phospholipids possess pro-health properties. They act neuroprotectively,regulate brain activity, improve memory and resistance to stress, reduce depression risk, Alzheimer and Parkinson diseases. Due to participation in molecular transport, they influence cell growth and development, speed up organism regeneration after great physical effort. The phospholipids limit cholesterol absorption from gastrointestinal tract, are effective in liver therapy (steatosis, alcohol intoxication). Moreover, they are inhibitors of proinflammation factors, pathogens of alimentary canal and cancers (e.g. of colon and adenoma). Alkiloglycerphospholipids – unique component of milk fat – stimulate immune system and protect tissues against toxic action of hydroxyl radicals that is generated during radiotherapy.

Am J Clin Nutr. 2012 Dec;96(6):1465-72.
Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial.
Cheatham CL, Goldman BD, Fischer LM, da Costa KA, Reznick JS, Zeisel SH.
Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 28081, USA. [email protected]

BACKGROUND: Choline is essential for fetal brain development, and it is not known whether a typical American diet contains enough choline to ensure optimal brain development.
OBJECTIVE: The study was undertaken to determine whether supplementing pregnant women with phosphatidylcholine (the main dietary source of choline) improves the cognitive abilities of their offspring.
DESIGN: In a double-blind, randomized controlled trial, 140 pregnant women were randomly assigned to receive supplemental phosphatidylcholine (750 mg) or a placebo (corn oil) from 18 wk gestation through 90 d postpartum. Their infants (n = 99) were tested for short-term visuospatial memory, long-term episodic memory, language development, and global development at 10 and 12 mo of age.
RESULTS: The women studied ate diets that delivered ∼360 mg choline/d in foods (∼80% of the recommended intake for pregnant women, 65% of the recommended intake for lactating women). The phosphatidylcholine supplements were well tolerated. Groups did not differ significantly in global development, language development, short-term visuospatial memory, or long-term episodic memory.
CONCLUSIONS: Phosphatidylcholine supplementation of pregnant women eating diets containing moderate amounts of choline did not enhance their infants’ brain function. It is possible that a longer follow-up period would reveal late-emerging effects. Moreover, future studies should determine whether supplementing mothers eating diets much lower in choline content, such as those consumed in several low-income countries, would enhance infant brain development.

Semin Cell Dev Biol. 2011 Aug;22(6):624-8.
The supply of choline is important for fetal progenitor cells.
Zeisel SH.
Nutrition Research Institute, School of Public Health and School of Medicine, The University of North Carolina at Chapel Hill, Kannapolis, NC 28081, United States. [email protected]

ABSTRACT: Fetal progenitor cells proliferate, migrate, differentiate and undergo apoptosis at specific times during fetal development. Choline is needed by these cells for membrane synthesis and for methylation. There is growing evidence that this nutrient also modulates epigenetic regulation of gene expression in both neuronal and endothelial progenitor cells, thereby modifying brain development. It is likely that these mechanisms explain why, in rodent models, maternal dietary intake of choline influences both angiogenesis and neurogenesis in fetal hippocampus, and results in life-long changes in memory function. This also may explain why women eating diets low in choline have a greater risk of having a baby with a birth defect. Choline is mainly found in foods that contain fat and cholesterol, and intake of such foods has diminished in response dietary advice from nutritionists and physicians. Forty years ago, diets commonly contained choline-rich foods but now women in the USA tend to eat diets low in choline content. Premenopausal women normally may require less choline in their diet than do men and postmenopausal women, because estrogen induces the gene for the enzyme catalyzing endogenous biosynthesis of the choline-containing phospholipid phosphatidylcholine. However, many women have a single nucleotide polymorphism (SNP) that blocks the induction of endogenous biosynthesis, thereby making them require more dietary choline. When these women eat diets low in choline, the supply of this nutrient to the fetus is likely to be inadequate, and may perturb progenitor cell proliferation, migration, differentiation and apoptosis.

Cent Nerv Syst Agents Med Chem. 2012 Jun;12(2):82-94.
Choline nutrition programs brain development via DNA and histone methylation.
Blusztajn JK, Mellott TJ.
Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 72 East Concord Street, L808, Boston, MA 02118, USA. [email protected]

ABSTRACT: Choline is an essential nutrient for humans. Metabolically choline is used for the synthesis of membrane phospholipids (e.g. phosphatidylcholine), as a precursor of the neurotransmitter acetylcholine, and, following oxidation to betaine, choline functions as a methyl group donor in a pathway that produces S-adenosylmethionine. As a methyl donor choline influences DNA and histone methylation–two central epigenomic processes that regulate gene expression. Because the fetus and neonate have high demands for choline, its dietary intake during pregnancy and lactation is particularly important for normal development of the offspring. Studies in rodents have shown that high choline intake during gestation improves cognitive function in adulthood and prevents memory decline associated with old age. These behavioral changes are accompanied by electrophysiological, neuroanatomical, and neurochemical changes and by altered patterns of expression of multiple cortical and hippocampal genes including those encoding key proteins that contribute to the biochemical mechanisms of learning and memory. These actions of choline are observed long after the exposure to the nutrient ended (months) and correlate with fetal hepatic and cerebral cortical choline-evoked changes in global- and gene-specific DNA cytosine methylation and with dramatic changes of the methylation pattern of lysine residues 4, 9 and 27 of histone H3. Moreover, gestational choline modulates the expression of DNA (Dnmt1, Dnmt3a) and histone (G9a/Ehmt2/Kmt1c, Suv39h1/Kmt1a) methyltransferases. In addition to the central role of DNA and histone methylation in brain development, these processes are highly dynamic in adult brain, modulate the expression of genes critical for synaptic plasticity, and are involved in mechanisms of learning and memory. A recent study documented that in a cohort of normal elderly people, verbal and visual memory function correlated positively with the amount of dietary choline consumption. It will be important to determine if these actions of choline on human cognition are mediated by epigenomic mechanisms or by its influence on acetylcholine or phospholipid synthesis.

Lipids Health Dis. 2011 Jan 28;10:25.
DL- and PO-phosphatidylcholines as a promising learning and memory enhancer.
Nagata T, Yaguchi T, Nishizaki T.
Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.

ABSTRACT: In the water maze test, oral administration with 1,2-dilynoleoyl-sn-glycero-3-phosphocholine (DLPhtCho)(5 mg/kg) alone or DLPhtCho (5 mg/kg) plus 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPhtCho)(5 mg/kg) significantly shortened the prolonged acquisition latency for rats intraperitoneally injected with scopolamine, with more efficient effect than (POPhtCho)(5 mg/kg) alone, arachidonic acid (AA)(5 mg/kg) alone, docosahexaenoic acid (DHA)(5 mg/kg) alone, or 1-palmitoyl-2-linoleil-sn-glycero-3-phosphoserine (PLPhtSer)(5 mg/kg) alone. POPhtCho (5 mg/kg) alone or DLPhtCho (5 mg/kg) plus POPhtCho (5 mg/kg) also significantly shortened the prolonged retention latency for rats intraperitoneally injected with scopolamine, but otherwise no significant effect was obtained with DLPhtCho (5 mg/kg) alone, AA (5 mg/kg) alone, DHA (5 mg/kg) alone, or PLPhtSer (5 mg/kg) alone. Oral co-administration with DLPhtCho (5 mg/kg) and POPhtCho (5 mg/kg) significantly shortened the acquisition latency for rats untreated with scopolamine as compared with the latency for administration with polyethylene glycol (PEG), DLPhtCho alone at doses of 5 and 10 mg/kg, or POPhtCho alone at doses of 5 and 10 mg/kg, while no efficient effect on the retention latency was obtained. To assess the effect of DLPhtCho and POPhtCho on cognitive functions for humans, Mini Mental State Examination (MMSE) test was performed in subjects with cognitive disorders (the average MMSE score, 15). Oral co-intake with DLPhtCho (50 mg) and POPhtCho (45 mg) once after breakfast everyday raised the score to over 20, corresponding to normal cognitive functions, throughout 5 months after intake, and the increase in the score was significantly greater than that for oral intake with DLPhtCho (100 mg/day) alone or POPhtCho (90 mg/kg) alone. Taken together, the results of the present study show that co-intake with DLPhtCho and POPhtCho could enhance learning and memory ability and improve cognitive disorders for both the animals and humans with a promising efficacy.

J Alzheimers Dis. 2011;27(2):327-39.
Neuroprotective effects of a specific multi-nutrient intervention against Aβ42-induced toxicity in rats.
de Wilde MC, Penke B, van der Beek EM, Kuipers AA, Kamphuis PJ, Broersen LM.
Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands. [email protected]

ABSTRACT: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly. Substantial evidence suggests a role for nutrition in the management of AD and especially suggests that interventions with combinations of nutrients are more effective than single-nutrient interventions. The specific multi-nutrient combination Fortasyn™Connect (FC), shown to improve memory in AD, provides phosphatide precursors and cofactors and is designed to stimulate the formation of phospholipids , neuronal membranes, and synapses. The composition comprises nucleotides, omega-3 polyunsaturated fatty acids (n3 PUFA), choline, B-vitamins, phospholipids, and antioxidants. The current study explored the protective properties of FC in a membrane toxicity model of AD, the amyloid-β 1-42 (Aβ42) infused rat, which shows reduced exploratory behavior in an Open Field and impaired cholinergic functioning. To this end, rats were fed an FC enriched diet or a control diet and five weeks later infused with vehicle or Aβ42 into the lateral ventricle. Ten weeks post-infusion Aβ42-rats fed the FC diet showed increased membrane n3 PUFA and phosphatidylcholine content while they did not show the reductions in exploratory behavior or in choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) immunoreactivity that were seen in Aβ42-rats fed the control diet. We conclude that FC protects the cholinergic system against Aβ42-induced toxicity and speculate that the effects of FC on membrane formation and composition might be supportive for this protective effect. Based on these data a long-term intervention study was started in the prodromal stages of AD

Rejuvenation Res. 2011 Dec;14(6):597-604.
Delivery of sesamol-loaded solid lipid nanoparticles to the brain for menopause-related emotional and cognitive central nervous system derangements.
Kakkar V, Mishra AK, Chuttani K, Chopra K, Kaur IP.
Department of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.

ABSTRACT: The physicochemical nature of sesamol (logP 1.29; solubility 38.8 mg/mL) substantially enhances its tissue distribution, minimizing its brain delivery. Sesamol-loaded solid lipid nanoparticles (S-SLNs) with an average particle size of 122 nm and an entrapment efficiency of 75.9 ± 2.91% were developed. Biochemical and behavioral paradigms clearly established the superiority of orally administered S-SLNs. The same was confirmed evidently by scintigraphic images of rabbits administered radiolabeled SLNs and confocal microscopy of brain sections of rats administered similarly prepared SLNs with a fluorescent marker. This study indicates the special importance of using phosphatidylcholine (as co-surfactant) in the preparation of SLNs for improving memory deficits. The aim of the present work was to develop sesamol as a therapeutic agent for central nervous system derangements.

Neurochem Int. 2010 Dec;57(8):935-9.
Hippocampal lipids linked to spatial memory in the C57BL/6J mouse.
Köfeler HC, Tiboldi A, Hoeger H, Lubec G.
Center for Medical Research, Medical University of Graz, Stiftingtalstraße 24, 8010 Graz, Austria.

ABSTRACT: Although the role of individual brain lipids for learning and memory has been reported, no systematic approach associating brain lipids with spatial memory has been carried out. It was therefore the aim of the study to determine brain lipids in hippocampus of mice forming and yoked controls that did not form spatial memory using the probe trial as the endpoint. 10 animals were trained in the Morris water maze (MWM) and 10 mice were serving as yoked controls i.e. no platform was used during the whole experiment. Hippocampal tissue lipids were extracted and data were acquired with Fourier transformation ion cyclotron resonance mass spectrometry (LTQ-FT) coupled to HPLC. Glycerophosphatidylethanolamines (18:0/22:6, 18:0/20:4 and 18:1/18:1), plasmalogens (16:0-10/22:6 and 18:0-10/22:6) and ceramides (18:0) showed higher levels in the trained group, while glycerolysophosphatidylcholines (16:0, 18:1, 18:0, 20:4), sphingomyelins (16:0, 24:1), ether linked glycerophosphatidylcholines (16:0-10/18:0), glycerophosphatidylcholines (16:0/18:1, 16:0/18:0, 18:0/18:1, 38:7, 18:1/20:1, 20:4/20:4, 22:1/18:1, 22:0/18:1, 20:4/22:6, 22:6/22:6), glucosylceramide (24:1) and plasmalogen (18:0-10/20:1) revealed lower levels in the trained group. Decreased levels of certain species of lysophosphatidylcholine, sphingomyelin, plasmenylphosphatidylcholine, phosphatidylcholine, glycosylceramide and plasmalogen at the probe trial for spatial memory may indicate catabolism in terms of consumption during this process. Increased hippocampal levels of long chain highly unsaturated phosphatidylethanolamines, plasmalogens and ceramides may reflect increased synthesis or decreased degradation at the endpoint of memory testing, probably representing interactions in the brain lipid pathways. The study shows pathways involved in spatial memory, may propose the use of individual brain lipids as probable cognitive enhancers and forms the basis for further studies on the role of brain lipids per se.

J Neurovirol. 2010 Nov;16(6):445-56.
Disturbance in cerebral spinal fluid sphingolipid content is associated with memory impairment in subjects infected with the human immunodeficiency virus.
Mielke MM, Bandaru VV, McArthur JC, Chu M, Haughey NJ.
Department of Psychiatry, Richard T. Johnson Division of Neuroimmunology and Neurological Infections, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.

ABSTRACT: Despite widespread use of antiretroviral therapies to control replication of the human immunodeficiency virus (HIV), dysfunctions of cognition that are collectively termed HIV-associated neurocognitive disorders (HAND) still occur in approximately 50% of those infected by the virus. Currently there is not a biomarker that can identify HIV-infected people who are at risk for the development of HAND. Previous studies have identified particular sphingolipid species that are dysregulated in HAND, but the neurocognitive correlates of these biochemical findings are not currently understood. To address this question, we compared cerebrospinal fluid (CSF) levels of sphingomyelin, ceramide, and sterol species with performance on standard neurological tests designed to assess the function of multiple cognitive and motor domains in HIV-infected subjects. We found that sphingomyelin:ceramide ratios for acyl chain lengths of C16:0, C18:0, C22:0, and C24:0 were associated with worse performance on several indices of memory. The most striking finding was for the acyl chain of C18:0 that consistently associated with performance on multiple tests of memory. These findings suggest that the sphingomyelin:ceramide ratio for C18:0 may be a reasonable surrogate marker for memory dysfunction in HIV-infected subjects.

J Neuropsychiatry Clin Neurosci. 2010 Summer;22(3):345-7.
A study of herbal remedies for memory complaints.
Serby MJ, Yhap C, Landron EY.
Beth Israel Medical Center, Department of Psychiatry, First Ave. at 16th St., New York, NY 10003, USA.[email protected]

ABSTRACT: This study explored the approach to marketing herbal substances and the specific remedies being sold for the treatment of memory complaints. Gingko and phosphatidylcholine/phosphatidylserine were most frequently recommended, often in combinations with many other substances. Counseling regarding toxicity is nil.

Acta Neurol Taiwan. 2009 Dec;18(4):231-41.
Essential fatty acids and human brain.
Chang CY, Ke DS, Chen JY.
Department of Neurology, Chi-Mei Medical Center, Tainan Taiwan. [email protected]

ABSTRACT: The human brain is nearly 60 percent fat. We’ve learned in recent years that fatty acids are among the most crucial molecules that determine your brain’s integrity and ability to perform. Essential fatty acids (EFAs) are required for maintenance of optimal health but they can not be synthesized by the body and must be obtained from dietary sources. Clinical observation studies has related imbalance dietary intake of fatty acids to impaired brain performance and diseases. Most of the brain growth is completed by 5-6 years of age. The EFAs, particularly the omega-3 fatty acids, are important for brain development during both the fetal and postnatal period. Dietary decosahexaenoic acid (DHA) is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Beyond their important role in building the brain structure, EFAs, as messengers, are involved in the synthesis and functions of brain neurotransmitters, and in the molecules of the immune system. Neuronal membranes contain phospholipid pools that are the reservoirs for the synthesis of specific lipid messengers on neuronal stimulation or injury. These messengers in turn participate in signaling cascades that can either promote neuronal injury or neuroprotection. The goal of this review is to give a new understanding of how EFAs determine our brain’s integrity and performance, and to recall the neuropsychiatric disorders that may be influenced by them. As we further unlock the mystery of how fatty acids affect the brain and better understand the brain’s critical dependence on specific EFAs, correct intake of the appropriate diet or supplements becomes one of the tasks we undertake in pursuit of optimal wellness.

Nutr Res. 2009 Jan;29(1):70-4.
Dietary supplementation with a combination of alpha-lipoic acid, acetyl-L-carnitine, glycerophosphocoline, docosahexaenoic acid, and phosphatidylserine reduces oxidative damage to murine brain and improves cognitive performance.
Suchy J, Chan A, Shea TB.
Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA.

Alzheimer disease has a complex etiology composed of nutritional and genetic risk factors and predispositions. Moreover, genetic risk factors for cognitive decline may remain latent pending age-related decline in nutrition, suggesting the potential importance of early nutritional intervention, including preventative approaches. We hypothesized that a combination of multiple nutritional additives may be able to provide neuroprotection. We demonstrate herein that dietary supplementation with a mixture of ALA, ALCAR, GPC, DHA, and PS reduced reactive oxygen species in normal mice by 57% and prevented the increase in reactive oxygen species normally observed in mice lacking murine ApoE when maintained on a vitamin-free, iron-enriched, oxidative-challenge diet. We further demonstrate that supplementation with these agents prevented the marked cognitive decline otherwise observed in normal mice maintained on this challenge diet. These findings add to the growing body of research indicating that key dietary supplementation may delay the progression of age-related cognitive decline.

J Nutr. 2008 Dec;138(12):2502-9.
Cognitive impairment in folate-deficient rats corresponds to depleted brain phosphatidylcholine and is prevented by dietary methionine without lowering plasma homocysteine.
Troen AM, Chao WH, Crivello NA, D’Anci KE, Shukitt-Hale B, Smith DE, Selhub J, Rosenberg IH.

Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111 ABSTRACT: Poor folate status is associated with cognitive decline and dementia in older adults. Although impaired brain methylation activity and homocysteine toxicity are widely thought to account for this association, how folate deficiency impairs cognition is uncertain. To better define the role of folate deficiency in cognitive dysfunction, we fed rats folate-deficient diets (0 mg FA/kg diet) with or without supplemental L-methionine for 10 wk, followed by cognitive testing and tissue collection for hematological and biochemical analysis. Folate deficiency with normal methionine impaired spatial memory and learning; however, this impairment was prevented when the folate-deficient diet was supplemented with methionine. Under conditions of folate deficiency, brain membrane content of the methylated phospholipid phosphatidylcholine was significantly depleted, which was reversed with supplemental methionine. In contrast, neither elevated plasma homocysteine nor brain S-adenosylmethionine and S-adenosylhomocysteine concentrations predicted cognitive impairment and its prevention by methionine. The correspondence of cognitive outcomes to changes in brain membrane phosphatidylcholine content suggests that altered phosphatidylcholine and possibly choline metabolism might contribute to the manifestation of folate deficiency-related cognitive dysfunction.

Current Pharmaceutical Biotechnology, Volume 7, Number 6, Dec 2006 455-455
Essential Fatty Acids
Das, Undurti N.
UND Life Sciences 13800 Fairhill Road, #321Shaker Heights OH 44120 USA.

ABSTRACT: This special issue of Current Pharmaceutical Biotechnology deals with an exciting topic: Essential Fatty Acids” and their implications for human health. Essential fatty acids (EFAs) are the main constituent of the phospholipid component of all cell membranes in the human body. EFAs, as its name implies, are essential for human survival but cannot be synthesized by the human body and hence, have to be obtained in our diet. The two EFAs are linoleic acid (LA) and -linolenic acid (ALA). Both LA and ALA form precursors to several of their long chain metabolites. Some of the important molecules that are formed from EFAs and their long-chain metabolites include: various eicosanoids, lipoxins, resolvins, and protectins. These molecules have several important actions on vascular tissue, platelets, leukocytes, macrophages, bronchial smooth muscle, myocardium, kidney, brain, and other cells and tissues in the body. Depending on the local tissue concentration and the type of metabolite formed from EFAs, they can have useful and harmful actions. For instance, excess formation of leukotrienes may produce inflammation, bronchospasm and thus may cause bronchial asthma. On the other hand, formation of appropriate amounts of lipoxins and resolvins may help in the resolution of inflammation and healing of wounds. In addition, EFAs may interact with nitric oxide and form nitrolipids that have potent biological actions. EFAs and their metabolites seem to have an important role in brain growth and development and memory formation and consolidation, participate in a variety of physiological and pathological processes.

Wei Sheng Yan Jiu. 2004 May;33(3):324-7.
[Effects of soybean phospholipids on learning and memory ability and contents of lipids in mice’s brain].
Gong J, Shi F, Shao L, Zheng X. [Article in Chinese]
College of Chemistry and Life Sciences Zhejiang Normal University, Jinhua 321004, China.

ABSTRACT OBJECTIVE: To study the effects of soybean phospholipids on learning and memory abilities and contents of protein and lipids in brain of mice. METHODS: Mice were randomly divided into four groups: low dose (2.5 g/kg), middle dose(5.0 g/kg) and high dose (10.0 g/kg) of soybean Phospholipids in diet and control group (distilled water). The mice were fed with soybean phospholipids everyday while control groups were fed with distilled water for 30 days. After learning and memory abilities were measured, the mice were killed and contents of protein, fatty acids and phospholipids in brain of mice were determined. RESULTS: The learning and memory abilities of mice fed with middle and high dose of soybean Phospholipids were improved obviously(P < 0.05), while memory abilities of low dose’s mice were stronger than that of control(P < 0.05). (2) The brain weight v.8 body weight of those in three doses’ group was obviously increased, and the protein content in brain was significantly higher compared with control(P < 0.05). (3) The contents of linoleic acid(C18: 2), linolenic acid(C18: 3) and ratio of polyunsaturated fatty acids(PUFA) to total fatty acids (TFA) obviously increased (P < 0.05). In brain of high dose mice, there was obvious change in the content of linolenic acid(C18: 3) in middle’s (P < 0.05). (4) The contents of phosphatidylcholine (PS) phosphatidylethanolamine (PE), Phosphatidylcholine (PC) and phospholipids (PL) obviously increase (P < 0.05), while ratio of SM to PC was decreased significantly in brain of high dose mice(P < 0.05). The contents of PS, PC and PL were increased obviously(P < 0.05). CONCLUSION: Soybean phospholipids may increase contents of protein, PUFA and PL in brain of mice and improve learning and memory abilities of mice effectively in a dose-response manner.

Life Sci. 1998;62(9):813-22
EGG phosphatidylcholine combined with vitamin B12 improved memory impairment following lesioning of nucleus basalis in rats.
Masuda Y, Kokubu T, Yamashita M, Ikeda H, Inoue S.
Q.P. Corporation, Department of Neuropsychiatry, Kochi Medical School, Tokyo, Japan.

We investigated the effects of egg phosphatidylcholine (PC) combined with vitamin B12 on memory in the Morris water maze task, and on choline and acetylcholine (ACh) concentrations in the brain of rats. Animals with nucleus basalis Magnocellularis (NBM) lesion received intragastric administration of egg PC or vitamin B12, or both for 18 days. Memory acquisition and retention were remarkably impaired in NBM lesioned rats compared with in sham-operated control. NBM lesioned group had lower choline and ACh concentrations than control group in the frontal cortex. High dose of egg PC alone significantly increased choline concentration, but did not change ACh concentration in the frontal cortex. High dose of vitamin B12 alone did not change choline and Ach concentrations in the brain. Either egg PC or vitamin B12 did not improve memory acquisition and retention. However, low dose of egg PC combined with vitamin B12 significantly increased ACh concentration and improved memory acquisition and retention in the NBM lesioned rats. We concluded that egg PC combined with vitamin B12 improved the memory impairment of NBM lesioned rats through the action on the cholinergic neurons.

J Nutr. 1995 Jun;125(6):1484-9.
Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia.
Chung SY, Moriyama T, Uezu E, Uezu K, Hirata R, Yohena N, Masuda Y, Kokubu T, Yamamoto S.
Department of Nutrition and Research Center of Comprehensive Medicine, University of the Ryukyus, Okinawa, Japan.

Studies on the effect of phosphatidylcholine administration on memory are limited. We administered egg phosphatidylcholine to mice with dementia and to normal mice and compared the differences in memory and serum choline concentration, and choline and acetylcholine concentrations and choline acetyltransferase activities of three forebrain regions (cortex, hippocampus and the remaining forebrain). Mice with dementia were produced by mating sibling mice who had impaired memory for > 20 generations. These mice had poor memory and low brain acetylcholine concentration. We administered 100 mg of egg phosphatidylcholine (phosphatidylcholine group) or water (control group) by gavage to each mouse daily for about 45 d. Control mice with dementia had poorer memory in passive avoidance performance and lower brain choline (cortex and hippocampus) and acetylcholine (hippocampus and forebrain excluding cortex and hippocampus) concentrations and lower cortex choline acetyltransferase activity than the control normal mice (P < 0.05). The administration of phosphatidylcholine to mice with dementia improved memory and generally increased brain choline and acetylcholine concentrations to or above the levels of the control normal mice. In normal mice, phosphatidylcholine treatment did not affect memory or acetylcholine concentrations in spite of the great increase in choline concentrations in the three brain regions. Serum choline concentration in mice treated with phosphatidylcholine increased to a similar level in both strains of mice, indicating that the absorption of phosphatidylcholine was not impaired in mice with dementia. The results suggest that administration of egg phosphatidylcholine to mice with dementia increases brain acetylcholine concentration and improves memory.

Neurosci Biobehav Rev. 1992 Summer;16(2):193-205.
Do essential fatty acids play a role in brain and behavioral development?
Wainwright PE.
Department of Health Studies, University of Waterloo, Ontario, Canada.

The membrane phospholipids of the brain contain high levels of polyunsaturated fatty acids (PUFA), particularly arachidonic acid, 20:4n-6 and docosahexaenoic acid, 22:6n-3. These long-chain PUFA are synthesized from their respective essential fatty acid (EFA) precursors, linoleic acid, 18:2n-6 and linolenic acid, 18:3n-3. Although the necessity of n-6 fatty acids for optimum growth has been established, a similar requirement for those of the n-3 family is less clear. The rapid accumulation of the long-chain n-3 PUFA in the brain during prenatal and pre-weaning development suggests that the provision of n-3 fatty acids to the developing brain may be necessary for normal growth and functional development. The intent of this review is to assess the experimental work which addresses this question, most of which has been conducted on rodents. The emphasis will be on studies which measure behavioral outcomes, and particular attention will be paid to methodological issues which affect the interpretation of these data. An integration of the research findings will be presented and discussed in light of possible implications for therapeutic interventions.

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