The binding of GM1 ganglioside to crude preparations of rat brain neuronal membranes was studied, the following results being obtained: (a) the binding process followed a biphasic kinetics, which displayed a break at 0.07-0.08 x 10(-6) M GM1 concentration; (b) the features of the binding process at GM1 concentrations below the break and, over the break, above 10(-6) M appeared to be different. Below the break the process proceeded slowly and brought a stable and irreversible association of GM1 molecules to the membranes. Over 10(-6) M the process was much more rapid and caused GM1 molecules to interact in such a way that they were releasable by washing and could exchange with newly added free ganglioside; (c) the two binding processes displayed the characteristics of a saturation phenomenon; (d) in both cases, GM1 taken up was freely available to galactose oxidase, indicating that the oligosaccharide chains protrude from the membrane surface. We postulate that GM1 occurs, below and above the break, in different physical forms, each of them having a different mechanism of interaction with the membrane. Above 10(-6) M GM1 interacts as micelles, and the basis of the micelle-membrane interaction is a fusion process. Below the break, in the 10(-8)--10(-7) M range, the binding is the result of hydrophobic interactions between sites on the membrane and the hydrophobic portion of individual ganglioside molecules, most likely in the monomeric form.

Modification of membrane composition and enzymatic activities both in total brain homogenate and purified synaptic plasma membrane of 3 and 24 month old rats has been investigated. Protein, cholesterol and phospholipid content and (Na+, K+)ATPase and 2',3' cyclic nucleotide phosphohydrolase activities were determined. The major changes occurred in the whole homogenate where a general increase in total protein and cholesterol content with age and a significant increase of the cholesterol/phospholipids molar ratio has been detected. In S.P.M. aging process induced a decrease of protein, cholesterol and phospholipids content associated with an increased membrane viscosity and a decrease of delta E. These data are consistent with a change in the structural organization and in the distribution pattern of different cell population in the aging brain. A possible artifactual effect of freezing on the reported parameter is also discussed.

Among cerebral functions, memory seems to be extremely sensitive to the aging process, particularly in the pathological condition. In this case memory decline is one of the first and more consistent symptoms observed.The similarities between the memory deficit induced by anticholinergic drugs and by elderly people have been the origin of the cholinergic hypothesis of geriatric memory.' Cholinomimetics and/or acetylcholine precursors have been tentatively used in geriatric patients to facilitate and improve memory function. Unfortunately the results obtained with this therapeutical approach have not been consistent. We now report the pharmacological effect of a natural compound, phosphatidylserine, on the v) L m .. L 3 n * 0 30 CONTROL ec-ps FIGURE 1. Effect of chronic treatment of BC-PS on EEG abnormalities in middle-aged rats.Rat chronically implanted with EEG electrodes were recorded for 30 minutes after 10 minutes of adaptation. EEG analyses were performed by computer. 504

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The present study was undertaken in order to better characterize the functional state of anterior pituitary gland in young and old rats by using prolactin secretion and incorporation of radioactive phosphate into phosphatidylinositol (PI) as markers. The in vitro incorporation of radiolabeled phosphate into anterior pituitary PI was significantly (p< 0.01) greater in young (3–5 months) than in aged (24–25 months) male Sprague-Dawley rats. No significant difference was found in the incorporation by pituitary tissue of ³²P into phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Also, the extent of prolactin secretion from isolated pituitary was significantly greater in young than in aged rats, while the prolactin pituitary content was significantly higher in aged animals. In vitro dopamine (DA) decreased the incorporation of ³²P into PI, both in young and old pituitary glands, and inhibited prolactin secretion into the incubation medium. Brain cortex-phosphatidylserine (BC-PS), a pharmacologically active purified phospholipid, capable of stimulating the dopaminergic system in the hypothalamus and of decreasing prolactin secretion both in humans and rats in vitro and in vivo, inhibited the incorporation of labeled phosphate into PI of pituitary glands from either young or old rats, but did not alter the prolactin secretion from the glands incubated in vitro. Baseline prolactin plasma levels did not differ significantly between young and old rats either when blood was collected from the trunk after decapitation or underwent sampling from chronically cannulated rats. Chronic administration of BC-PS (15 mg/kg i.p. for 30 days) had a similar effect on prolactin plasma levels both in aged and young rats, while the phosphate incorporation into PI was significantly decreased only in young rats’ pituitaries. All together these data support the view that unchanged prolactin levels observed in old rats is the results of some adaptive compensatory mechanisms involved in the control of prolactin secretion.