PS/

Phosphatidylserine:(PS) _______________________
This substance is a major fatty substance in the brain where it plays a major role in determining the integrity and fluidity of cell membranes. Normally the brain can manufacture sufficien levels of PS but if there is a deficiency of folic acid, vitamin B12 or essential fatty acids the brain may not be able to make sufficient quantities. Low levels of PS in the brain are associated with impaired mental function and depression. In the largest double blind study a total of 494 elderly patients between the age of 65 and 93 with moderate to severe senility were given either PS or a placebo for 6 months. The patients were assessed for mental performance, behavior and mood at the beginning and at the end of the study/ Statistically significant improvements were noted in the PS group as compared to the placebo group. Unlike typical anti-depressants PS promoted this improvement without influencing the levels of serotonin and other monoamine neurotransmitters, suggesting another mechanism of action. Improved neuron cell membrane fluidity may be one explanation. Another is the fact that PS has been shown to reduce cortisol secretions in response to stress. Typically cortisol levels will be elevated in depressed patients. Lowering the cortisol level restores proper brain chemistry. PS is not abundant in common foods, so it is limited in the human diet. Moreover the body can make it only thru a compex series of reactions and with substantial investment of energy. Given oraly PS is rapidly absorbed and readily crosses the blood brain barrier to reach the brain. There its sites of action appear to be exclusively in the cell membrane. Membranes are the major work surfaces of all known cells and nerve cells especially depend on membranes to carry out their specialized functions. The generation of the electrical current, the transmission of the current along the cell and the relaying of the current across the cell to cell synapse are all membrane driven events. Membrane proteins play key roles in all these processes and PS is important for regulating the activities of such proteins. PS and other phospholipids are large lipid molecules that hold together the diversity of large molecules in the cells membrane systems. The phospholipids pack together side to side and in a two layer molecular sandwich(a bilayer) creating a membrane matrix into which the proteins and and other membrane constituents are inserted and secured. The phospholipids of the membrane are a solvent for the proteins of the membrane. PS phopholipids are one of five PL classes that fulfill these physico-chemical functions. The others are Phosphotidylcholines(PC), ethanoalamines(PE), and inositols and sphingomeyelins which have a molecular organization different from the phosphatidyls. Nerve cell functions that have been linked to PS include the conduction of the nerve impulse, the accumulation, storage and release of the nerve trasmitters; and nerve transmitter action by way of "receptors" located on the target cell surface. The membranes of nerve cells are particularly high in PS. The outermost membrane of the cell, the cell membrane is a kind of master switch for the cell. Amoung those cell functions which the cell membrane are in control of: a)Entry of nutrients into the nerve cell b)Movements of charged atoms(ions) into and out of the cell c)Passage of molecular messages from outside the cell into the cytoplasm d)Cell movement, shape changes, flattening or expansion e)Cell to cell communication The membrane based ion pumps, transport enzymes and receptors which manage these master switch activities are proteins, but all depend on the PL membrane matrix for their full functional capacity and for their coordinated activity. PS seemingly has the specialized function of helping to anchor many of these proteins in the matrix. Also PS carries a negaively charged amino headgroup which tends to associate preferentially with ATPases, kinases, receptors and other key membrane proteins. These specific PS-protein associations may be the ultimate key to the remarkable global effects of PS on the brain as a whole Reference->Pepeu et al, 1996"A review of phosphatidylserine pharmacological and clinical effects. Is phosphatidylserine a drug for the aging brain? Pharmacol Res 33(2),73-80 PS facilitates an array of cell functions that build on membrane functions. a)Maintainence of the cells internal environment:PS in the cell membrane of the neurons is essential for the ATPase enzymes that regulate cellular sodium-postassium and calcium magnesium balance. Due to their constant electrical activity, generated by ion movement across their membranes, nerve cells rely heavily on the ATPase enzymes. In cell membrane preparations isolated from the brains of aged rats treated with PS, the cholesterol/phospholipid ratio and ATPase activities were found to be reversed towards values characteristic of younger rats. b)Signal Transduction: PS is known to regulate the binding of opiates and glutamine to their receptors, to enhance the olfactory bulb sensitivity in turtles, and to restore prolactin receptor density in aging rats. c)Secretory vesicle release: Most cells secrete hormones, nerve transmitters or other materials to the outside environment by way of the membrane coated micro-packages called secretory vesicles. In fact, vesicle secretion is the major means by which nerve transmitters are released from the nerve cell axon endings. PS may help prepare the cell membrane and or the vesicle membrane for the two to fuse with each other and brain decline are unique to the PS molecule. -other phospholipids did not effectively substitute for PS in such experiments, nor did the amino acid serine. Bioavailability of PS Cenacchi and collaborators reviewed lab findings from 130 subjects given 300 mg. of PS daily for up to 60 days during clinical trials. They found a lowering of uric acid levels and liver SGPT. Phosphatidylserine has good bioavailability by the oral route. Following oral dosing to rats, radioactively labeled PS appears in the blood at about 30 minutes. After a few more minutes uptake begins into the liver and later the brain. References: ___________ Cenacchi T et al:Cognitive decline in the elderly,a double blind placebo controlled study on the efficacy of ps admin. Aging 5:123-33 1993 Engel RR et.al Effects of phosphotidylserie in Alzheimers disease. Psychoparmacol Bull 28:61-6 1992