ReviewPhosphatidylserine and the human brain
Introduction
Phosphatidylserine (PS) is the major acidic phospholipid in human membranes and constitutes 2% to 20% of the total phospholipid mass of adult human plasma and intracellular membranes [1], [2], [3]. Within the healthy human brain, myelin is enriched in PS [4], [5] and the PS content of gray matter doubles from birth to age 80 y [4]. Throughout the human body, PS is a structural component of endoplasmic reticulum, nuclear envelopes, Golgi apparati, inner (cytosolic) leaflets of plasma membranes, outer mitochondrial membranes, and myelin [1], [2], [3], [4], [5], [6], [7], [8], [9].
About 20% to 30% of the PS in human gray matter is in the form of 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphoserine [4], [10], [11], [12], [13]. The docosahexaenoic acid (DHA) content of neuronal PS is of functional importance [12]; in the cortex of the brain, a reduction in the DHA content of PS is associated with the progression of mild cognitive impairment to Alzheimer's disease [14]. Consequently, the incorporation of PS into human membranes is sensitive to the availability of both PS and DHA [4], [10], [11]. Additionally, fatty-acid recycling at the sn-1 and sn-2 positions of PS is frequent, rapid and energy-consuming, allowing co-accumulation of DHA and PS [10], [11], [15] and facilitating DHA enrichment of PS molecules within membranes [11].
Section snippets
Phosphatidylserine synthesis and incorporation into membranes
Most PS that is synthesized de novo, including that synthesized within the central nervous system, results from the PS synthase 1- (PSS1-) catalyzed substitution of serine for choline on PS within mitochondria-associated membrane (MAM) domains of the endoplasmic reticulum (ER) [13], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25]. Some newly synthesized PS is transported from the ER to the inner (cytosolic) leaflet of the plasma membrane [1], where thermodynamic barriers minimize its
Phosphatidylserine and neurotransmission
The incorporation of PS into neuronal cell membranes influences the metabolism of the neurotransmitters acetylcholine (ACh), norepinephrine, serotonin, and dopamine [63], [64], [65]. Adequate amounts of DHA-enriched PS are required for the fusion of intraneuronal secretory granules with the presynaptic membrane, the subsequent release of neurotransmitter molecules into the synaptic cleft during the intracellular transmission of action potentials and proper postsynaptic neurotransmitter-receptor
Aging and deterioration of the human brain
Aging of the human brain is associated with loss of neurons, dendritic atrophy, loss of synaptic connections, decreased synaptic density, decreased synthesis of ACh and other neurotransmitters, abnormal neuronal membrane lipid composition (especially decreased membrane PS content and increased membrane cholesterol content), and reduced sensitivity of postsynaptic membranes to ACh [63], [64], [75], [76], [77], [78], [79], [80], [81]. A decrease in the ratio of PS to cholesterol within neuronal
Phosphatidylserine in the deteriorating brain
In intact aged rats, ingested PS increases interneuronal communication by increasing the fluidity of cell membranes [59], [63], [64], eliminates the typical age-dependent decreases in stimulus-evoked ACh release, cholinergic functioning, and cognitive problem solving [82], [83], [84], and stimulates enhanced performance on tasks that test learning ability and short-term memory [82], [85], [86], [87]. These beneficial outcomes have been associated with rapid incorporation of supplemental PS into
Safety of dietary supplementation with phosphatidylserine
In addition to the absence of reports in the published scientific literature of adverse reactions concerning oral supplementation with PS, the safety of dietary supplementation with PS has been demonstrated in many human clinical trials [57], [63], [65], [93], [94], [95], [96], [97], [98], [99], [100], [101], [102], [103], [104], [105], [106], [107], [108], [109], [110], [111], [112], [119], [120], [121], [122], [123], [124], [125], [126], [127] and has been documented in detail by several
Conclusions
Phosphatidylserine is required for healthy nerve cell membranes and myelin. Oral PS is absorbed efficiently in humans and crosses the blood–brain barrier following its absorption into the bloodstream, increasing the supply of PS to the brain. Increasing the supply of PS increases the incorporation of it into neuronal cell membranes. The incorporation of adequate amounts of PS within nerve cell membranes is required for efficient neurotransmission throughout the human nervous system.
Aging of the
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