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Biomedical subjects

M Brunetti

Publications and source records attributed to M Brunetti.

At least 73 records · Page 4Linked to original sources
PubMed1986

Biochemical studies on the nootropic drug, oxiracetam, in brain.

The aim of this work was to study the effects of the nootropic drug oxiracetam, on lipid metabolism in rat brain. Twenty-month-old rats and spontaneous hypertensive (SHR) rats with cerebrovascular lesions were used, which showed an impaired learning and memory rate if challenged with behavioral tests. Oxiracetam improves the in vitro and in vivo synthesis of phosphatidylcholine (PhC) and phosphatidylethanolamine (PhE) impaired by aging, when respectively added to the incubation medium or administered subacutely to animals. SHR rats drinking saline, and with cerebrovascular lesions, have a reduced choline incorporation into cerebral phospholipids and an increase of arachidonic acid release from the same lipids if compared to SHR rats (without cerebrovascular lesions) drinking water. They also show a decreased incorporation rate of arachidonic acid into PhC, PhE, and PhC plasmalogen and PhE plasmalogen. If oxiracetam is chronically administered (200 mg/kg/day for 14 weeks) a significant variation in the incorporation of both precursors takes place. In the first 2 h after the intracerebroventricular (i.c.v.) injection of choline and arachidonic acid the values are comparable to those observed in SHR rats with lesions; at longer time intervals, however, the rates of incorporation are similar and even better than those of SHR rats without lesions. Since the drug does not seem to influence the incorporation of the precursors in the first 2 h after their administration, we may assume that oxiracetam acts on the turnover of the phospholipids more than on their rate of synthesis from injected precursors.

Aging↗
PubMed1985

Effect of chronic treatment with phosphatidyl serine on phospholipase A1 and A2 activities in different brain areas of 4 month and 24 month old rats.

The activities of phospholipase A1 and A2 were tested in mitochondria and microsomes from different cerebral areas of both 4 month and 24 month old rats, after 30 days i.p. treatment with ox Brain Cortex Phosphatidyl Serine (BC-PS). In the brain areas from control animals a rather great decline in its ability to hydrolize the fatty acids of the main phosphoglycerides was found. Taking into account only the effect of treatment with BC-PS on the modification of phospholipase activities caused by aging, we found that the treatment was able to balance the enzymatic functions altered by aging in several of the area examined. The importance of this result on the lipidic metabolism of the aging brain is also discussed.

Aging↗
PubMed1984

Turnover of ethanolamine phosphoglycerides in different brain areas of adult and aged rats.

The turnover of ethanolamine glycerophospholipids (EGP) has been determined in six different cerebral areas of 4-month and 22-month-old rats, by injecting [3H]glycerol together with [14C]ethanolamine into the lateral ventricle of the brain. The areas examined behave quite differently in respect to their utilization of the most simple precursors of phosphoglyceride biosynthesis. The incorporation of both glycerol and ethanolamine is already complete as early as 2-4 hours and then reutilization begins, at least for the so called fast pools of phosphoglycerides. The different slopes of the specific activity of the two precursors in EGP suggest a high degree of variance among catabolic rates in the different brain regions. In aged rats the utilization of the water-soluble precursors of EGP synthesis decreases in all brain areas and these data suggest that aging may have a different effect on the catabolic activities as well as phospholipid biosynthesis.

Age Factors↗
PubMed1982

The synthesis in vivo of choline and ethanolamine phosphoglycerides in different brain areas during aging.

The biosynthesis of choline and ethanolamine phosphoglycerides was tested in vivo in different brain areas of the rat during aging. Mixtures of [2-3H] glycerol and [Me-14C] choline or [2-3H] glycerol and [2-14C] ethanolamine were injected into lateral ventricle of the brain as lipid precursors and their incorporation into corresponding phospholipid was examined. A significant decrease of synthesis of both phosphoglycerides takes place in cerebral cortex and in the striatum, and is already apparent at 9 months of age with no further decrease or change thereafter. No significant change takes place in the cerebellum. The unchanged absorption of injected water-soluble precursors, together with the lack of any significant change of phospholipid/protein ratio in all examined brain areas, suggests that the incorporation of both glycerol and nitrogen bases are affected by aging.

Aging↗
PubMed1981

Contribution of axonal transport to the renewal of myelin phospholipids in peripheral nerves. II. Biochemical study.

The classes of radioactive phospholipids appearing in the ciliary ganglion (CG) and especially in the myelin sheath of the intraorbital part of the oculomotor nerve (OMN) were determined after the intracerebral injection of [2-3H]glycerol and [methyl-14C]choline to chickens. Analysis of the radioactive compounds in water-soluble fractions and chloroform-methanol extracts was performed by thin-layer chromatography (TLC). The water-soluble content of the OMN and CG was much poorer in [2-3H]glycerol and metabolites than in [methyl-14C]choline and derivatives. All classes of glycerophospholipids were found to be axonally transported along the OMN and into the CG, but choline-phosphoglycerides (CPG) were largely predominant. In myelin fractions from the OMN, the specific radioactivity (SRA) of CPG labeled with [2-3H]glycerol reached a maximum earlier (40 h) than the SRA of CPG labeled with [methyl-14C]choline. A 25-fold enhancement of the [14C]SRA of sphingomyelin (SM) was observed between 12 h and 7 days. These results indicate that: (1) axonally transported phospholipids labeled with [2-3H]glycerol consist mainly of CPG; (2) small amounts of CPG are translocated from the axon to myelin; and (3) the progressive enrichment of myelin in [14C]CPG and, to a greater extent, SM draws attention to the importance of the base recycling for local synthesis of myelin phospholipids. Thus the axonal supply of Schwann cells with choline and the transfer of axonal phospholipids to myelin would probably contribute to the metabolic interdependence existing between neuron and glia.

Animals↗
PubMed1981

Phospholipid metabolism in neuronal and glial cells during aging.

The incorporation of cytidine-containing precursors (CDP-Cho and CDP-Etn) into the main phospholipid classes of cellular fractions enriched in neurons and glial cells from whole rat brains of different ages was examined. The rate of synthesis of choline phosphoglycerides in neuronal homogenates significantly decreased with age up to 18 months; after this time no additional decrease was found. The decrease of CDP-Etn incorporation in neurons was found to be less significantly affected by age up to 18 months, but the enzymic activity decreased after 18 months of age. No changes were found in the corresponding glial activity at any age. Biochemical phenomena that occur in 18-month-old rat brain (aged animals) were compared with phenomena occurring in 2-month-old rat brain (adult animals). No significant variations of lipid composition were found in neurons from either 18-month-old or 2-month-old rat brain. These results, together with some kinetic parameters, suggest that ethanolamine and choline phosphotransferases are affected differently by aging.

Aging↗
PubMed1979

Synthesis of phosphatidylcholine and phosphatidylethanolamine at different ages in the rat brain in vitro.

The de novo synthesis of choline and ethanolamine phosphoglycerides in brain microsomes from 18 month-old male rats was investigated in vitro by using labeled cytidine-5'-diphosphate choline and cytidine-5'-diphosphate ethanolamine as lipid precursors. The rate of synthesis of the two phospholipid classes was found to be noticeably decreased, as compared to that of adult animals. The addition of exogenous diacyl glycerols to microsomes from ageing rat brain brings the rate of synthesis nearly to the adult levels. The synthesis of choline and ethanolamine phosphoglycerides is not affected in the liver microsomes of ageing rats. The molar distribution of fatty acids in brain microsomal diacyl glycerols of ageing rats is noticeably different from that of adult animals. The content of monoenoic and dienoic species is increased, whereas that of the tetraenoic species is decreased. Base exchange reaction for choline and ethanolamine incorporation into respective phospholipids is not affected in the brain microsomes of the aged rats.

Aging↗
PubMed1978

Membrane-bound base-exchange reactions in animal tissues.

The calcium-stimulated incorporation of ethanolamine, L-serine and choline into rabbit synaptosomal phospholipids in vitro has been investigated. The synaptosomal membranes were prelabelled in vitro in their choline-, ethanolamine- or serine-phosphoglycerides by base-exchange and then chasing experiments were performed by displacing the lipid-bound base by ethanolamine, choline or L-serine labelled with a different isotope. The results indicate that membrane phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine are substrates for the exchange with all the three mentioned bases. A very small phospholipid pool (0.5-2% of the total available pool) is active in the calcium-dependent exchange between membrane phosphatidylcholine or phosphatidylethanolamine and free bases, whereas the pool of exchanging phosphatidylserine is sensibly larger (2-9%). In another series of experiments the effect of the base-exchange reaction upon the production of cyclic-AMP at the level of rat brain synaptic membranes has been examined. An exchange with ethanolamine produces a significant decrease of the NaF-stimulated production of the cyclic nucleotide, whereas it increases the noradrenaline-induced production. With some exceptions, the exchange with L-serine produces opposite effects. The possible physiological importance of phospholipid pool at the synaptosomal level is discussed.

Adenylyl Cyclases↗
PubMed1976

Relationships between base-exchange reaction and the microsomal phospholipid pool in the rat brain in vitro.

The calcium-stimulated incorporation of ethanolamine, choline and L-serine into rat brain microsomal phospholipids has been investigated. The membranes were prelabeled in vitro in their choline or serine phosphoglycerides by base-exchange and then chasing experiments were done by displacing the lipid-bound base by ethanolamine, choline, or L-serine labeled with a different isotope. The results indicate that membrane phosphatidylcholine is presumably a substrate for the exchange with all the three bases, whereas phosphatidylserine exchanges only with ethanolamine and L-serine but not with choline. A small phospholipid pool (3-7% of the total available pool) is active in the calcium-dependent exchange with choline, ethanolamine, and L-serine. When the microsomal membranes are prelabeled in vitro in their phosphatidylcholine moiety through the cytidine-dependent pathway and then chasing experiments are performed with the three nitrogenous bases, as above, the small phospholipid pool is hardly detectable. In view of these and other results (Gaiti et al., FEBS Letters 49:361 1975), it is suggested that at least two different pools of phosphatidylethanolamine, phosphatidylserine, and phosphatidylcholine might exist in rat brain microsomes.

Animals↗