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Biomedical subjects

G Trovarelli

Publications and source records attributed to G Trovarelli.

At least 19 recordsLinked to original sources
PubMed1992

Arachidonic and palmitic acid utilization in aged rat brain areas.

We have previously demonstrated that the arachidonic acid (20:4) incorporation into brain lipids differs according to the age of the animals used and the experimental conditions adopted. These differences led to a further investigation of arachidonic acid uptake in both aged and adult rat brains, its transformation into CoA derivatives, its incorporation into diacyl-glycerols and polar lipids, and finally its oxidation to CO2. These metabolic parameters were then compared with those obtained after using the saturated fatty acid palmitate (16:0). In both cases slices or mitochondria from different brain areas of 24-month-old and 4-month-old rats were examined. The results obtained indicate that the uptake of the fatty acids into cells is not modified by age. However, the successive metabolic transformations of the acids are altered to a considerable extent. In particular, in 24-month-old animals (compared with 4-month-old rats) there is a significant decrease of 20:4 in its incorporation into lipids as well as its oxidation to CO2, while arachidonoyl-CoA content increases by about 50%. This increased amount of CoA derivative, which has a potent detergent effect, may interfere with membrane structure and affect membrane physiological functions. Furthermore, because the free arachidonate pool is maintained in a dynamic equilibrium with its esterified forms, the final result may be a perturbation of this equilibrium.

Aging↗
PubMed1987

Effect of cytidine on the modification of phospholipid metabolism induced by ischemia.

[1-14C-]Arachidonic acid was injected into the lateral ventricle of the gerbils (meriones unguiculatus) two hours before producing brain ischemia by the bilateral ligation of the carotid arteries. Ten minutes before the carotid ligation a group of animals received an additional intraventricular injection of cold cytidine (2.5 mumol/brain). Control animals with and without cytidine, together with the ischemic group, were decapitated directly into liquid nitrogen ten minutes after carotid ligation or sham surgery. Cytidine is able to both stimulate arachidonic acid incorporation into lipids and noticeably correct the release of this acid from polar lipids induced by ischemia. Based on these findings, it is possible to assume that cytidine exerts an effect on the biosynthesis of phosphoglycerides as well as on their catabolic activities.

Animals↗
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

Mature and immature synaptosomal membranes have a different lipid composition.

Subfractionation of the optic tectum in chick embryos results in the isolation of two fractions enriched in synaptosomes (fraction A and fraction B). In chicks after hatching, this fractionation results in the isolation of a single synaptosomal fraction (fraction B) and of a fraction enriched in myelin membranes devoid of synaptosomes (fraction A). The lipid composition of synaptosomal fractions (A and B) and corresponding synaptosomal plasma membranes has been analyzed and compared to the lipid composition of similar fractions isolated from 2-3 day-old chicks. The phospholipid composition of fraction A in embryos was mainly represented by phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The PE content was significantly lower than that of PC, which accounted for by approximately 50%. Sphingomyelin (SP) and phosphatidylinositol (PI) accounted for by only 6% of the total membrane phospholipids. Fraction A isolated from the young chicks showed many significant changes. PC accounted for by approximately 40% and PE made up 35%. The amount of phosphatidylserine (PS) and SP increased. These data parallel our previous morphological observations, which showed that fraction A contains immature synaptosomes in embryos but myelin membranes and no synaptosomes in the young chicks. Fraction B has been shown to contain synaptosomes at all stages considered. It possessed in embryos a lipid composition similar to fraction A, except that PC content was higher in young embryos. The analyses on membrane fractions confirmed these results. On the contrary, this fraction showed many significant changes after hatching. The content of PC was significantly reduced, PE/PC ratio was significantly increased as well as ethanolamine plasmalogen (PLE) content. The percentage of PS, PI and SP were increased. The composition of fatty acids of the total fraction of phospholipids was also examined. The results parallel the observations on phospholipid classes.

Age Factors↗
PubMed1984

The effect of cytidine-diphosphate choline (CDP-choline) on brain lipid changes during aging.

Lipid synthesis has been tested in vivo in different brain areas of 12-month-old male rats. Cortex, striatum, brainstem, and subcortex of brain have been examined. The cerebellum was discarded. Mixtures of (2-3H)glycerol and (Me-14C)choline were injected into the lateral ventricle of the brain as lipid precursors, and their incorporation into total lipid, water-soluble intermediates and choline-containing phospholipids was examined 1 hr after isotope injection. In another series of experiments cytidine-5'-diphosphate choline (CDP-choline) was injected intraventricularly to the aged rats 10 min before sacrifice with a simultaneous injection, and radioactivity assays were performed as above. Distribution of radioactivity content of CDP-choline among brain areas 10 min after its administration showed a noticeable enrichment of the nucleotide and water-soluble-related compounds in the examined areas, but to a lesser degree in the cerebral cortex. The incorporation of labelled glycerol, which is severely depressed in aged rats in all four areas [Gaiti et al, 1982, 1983], was increased only in the cortex, and apparently decreased in the other areas. This last result is probably due to a dilution effect brought about by the administered cold CDP-choline upon the (14C)-containing water-soluble metabolites. As a consequence, the (3H)/(14C) ratio in total lipid and in isolated phosphatidylcholine and choline plasmalogen increased after CDP-choline treatment.

Aging↗
PubMed1984

The influence of cytidine on the endogenous pool of CDP-choline, CDP-ethanolamine, and CMP of the rat brain.

Cold cytidine was intraventricularly administered into the brain of young rats, and its effect on CDP-choline, CDP-ethanolamine, and CMP pools followed for different time intervals and with various amounts of administered cytidine. The injected nucleoside produces a measureable increase of th concentrations of all three nucleotides. The increase produced by injecting 2.5 mumol of cytidine for brain does not essentially change with higher doses of injected nucleoside, except for CMP, whose increase reaches a maximum with 5 mumol of cytidine. A clear time dependence on cytidine administration was shown. The increases of the three nucleotide concentrations do not show a maximum till 60 min from administration into CMP and CDP-bases and measurably increases their endogenous brain pools. The compound is likely to enter metabolic events connected with phospholipid metabolism in brain.

Animals↗
PubMed1984

Abnormalities of the erythrocyte membrane phospholipids in Friedreich's ataxia.

The phospholipid composition and the fatty acids of the phospholipids in the erythrocyte membranes were studied in 5 patients with Friedreich's ataxia. The sphingomyelin content was found to be insignificantly reduced, that of phophatidylethanolamine was, on the contrary, increased even if non-significantly. The linoleic acid content was significantly decreased both in the total fraction of the phospholipids and in the isolated phosphatidylcholine. The relationship between the phospholipid composition and the structure and function of the membrane are discussed.

Adolescent↗
PubMed1983

The effect of S-Adenosyl-L-methionine on ischemia-induced disturbances of brain phospholipid in the gerbil.

Brain ischemia was produced in gerbils (Meriones unguiculatus) by the bilateral ligation of the carotid arteries with reported procedures. Changes in the energy status of brain demonstrated that carotid ligation was effective. At different time intervals from ligation, groups of gerbils were given either saline of S-Adenosyl-L-methionine (SAMe) by the intraventricular (i.v.) route (1.6 mg/Kg body wt. twice, at each 10 min interval), or by the intraperitoneal (i.p.) administration (200 mg/Kg body wt.) or subcutaneously (s.c.) with 40 mg/Kg body wt, daily, for two weeks. Control animals, with and without SAMe, together with the ischemic groups, were decapitated directly into liquid nitrogen, 10 min after ligation. Brain neutral and polar lipid, together with free fatty acids, which were all labeled in vivo by the intraventricular injection of [1-14C]arachidonic acid 2 hr prior to ligation, were extracted, purified and separated by conventional procedures. SAMe when injected i.v. or i.p. noticeably corrected the changes in polar lipid by reversing the decrease of brain phosphatidylcholine and choline plasmalogen, as well as of their labeling, which was due to ischemia. Concurrently with this action, SAMe treatment (i.v. and i.p.) also provided to some extent to re-establish the normal level of labeling of ethanolamine lipids. When SAMe was given s.c., no effect was present. SAMe had no effect on the increase of free fatty acid and diglyceride due to ischemia. The prevention by SAMe of the changes of choline lipids suggests that a stimulation of the methyltransferase reaction may occur in the ischemic brain, due to increased substrate (SAMe) availability. This effect may be important for cell survival, since membrane phospholipid derangements alter the properties of the membrane.

Animals↗
PubMed1982

The transport of cytidine into rat brain in vivo, and its conversion into cytidine metabolites.

Double-labeled cytidine, with a 3H/14C isotope ratio of 20.00, has been intraventricularly injected into the brain of young rats, and its fate followed up to 90 min from administration together time-course of labeling. The injected nucleoside enters the brain as an intact molecule and is immediately utilized without prior degradation. Cytidine is actively converted into uridine and CMP, the latter being then transformed by a stepwise mechanism into CDP and CTP, and finally into CDP-choline and CDP-ethanolamine. The results indicate that administered cytidine represents a compound likely to enter metabolic events, which lead to CDP-choline and CDP-ethanolamine synthesis, and presumably to phospholipid production.

Animals↗
PubMed1982

The influence of CDP-choline on brain lipid metabolism during ischemia.

The intraperitoneal administration of CDP-choline to gerbils (Meriones unguiculatus) partially prevented the changes of lipid metabolism found in brain after ischemia due to carotid occlusion. The increase of diglyceride pool and of its content of radioactivity, due to arachidonate labelling, was almost completely corrected by the treatment. The increase of the free fatty acids, due to ischemia, was unaltered. The decrease of the phosphatidylcholine labelling due to ischemia was partially corrected by the administered CDP-choline.

Animals↗
PubMed1981

Effect of cytidine diphosphate choline (CDP-choline) on ischemia-induced alterations of brain lipid in the gerbil.

Brain ischemia was produced in gerbils (Meriones unguiculatus) by the bilateral ligation of the carotid arteries. Definite changes in the energy status of brain demonstrated that carotid occlusion was effective. Five minutes before ligation, an intraventricular injection of either saline or cytidine disphosphate choline (CDP-choline, 0.6 micromol/brain, 3 microliter) was given to groups of animals. Control animals, with and without CDP-choline, together with the ischemic groups, were decapitated directly into liquid nitrogen; 10 min after arterial ligation. Brain free fatty acids, neutral lipids and phospholipids, which were labeled in vivo by the intraventricular injection of [1-14C]arachidonic acid (0.4-0.6 micro Ci, 6-9 nmol) 2 hr prior to ligation, were extracted, purified, and separated by thin-layer chromatographic procedures. The CDP-choline treatment noticeably corrected the increase of total and individual fatty acids due to ischemia and the increase of their radioactivity content. The changes in neutral lipids, particularly in the diacyl glycerol fraction, were also corrected by the injection of the nucleotide. CDP-choline partially reversed the decreased of brain phosphatidylcholine and of its labeling, which was due to ischemia. All the data indicate that the prior injection of CDP-choline stimulates the choline phosphotransferase reaction of brain towards synthesis of phosphatidylcholine and prevents the release of free fatty acids, particularly of arachidonic acid, associated with ischemia.

Animals↗
PubMed1980

Synaptosomal phospholipid pool in rabbit brain and its effect on GABA uptake.

Rabbit synaptosomes have been used to study the effect of the base-exchange reaction in membrane phospholipids on gamma-aminobutyric acid (GABA) transport in vitro. The uptake of GABA was measured after a base-exchange reaction with ethanolamine, choline, or L-serine and after subsequent displacement of these exchanged moieties from lipid by bases of similar or different structures which were added to the synaptosomal medium. Serine incorporation stimulated GABA transport, but its displacement from membrane lipid by choline or ethanolamine induced an inhibition of GABA transport. Ethanolamine incorporation inhibited GABA transport, but its displacement of serine or choline resulted in stimulation of GABA uptake. Choline incorporation also inhibited GABA transport, although less than ethanolamine. The pool size of synaptosomal phospholipids, presumably involved in GABA uptake, accounted for 0.2 to 10% of the total content of membrane phospholipid. Thus, alteration of phospholipid composition by exchange of the lipid hydrophilic head-groups influences the extent of GABA uptake into rabbit synaptosomes.

Animals↗
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↗
PubMedDate not supplied

The effect of oxiracetam treatment on alterations of lipid metabolism in brain areas from spontaneously hypertensive rats.

It has been previously demonstrated that spontaneously hypertensive adult rats (SHR) develop severe hypertension and cerebrovascular lesions on drinking 1% NaCl from weaning and that the phospholipid metabolism in the whole brain is actively altered in these lesioned animals (SHR-NaCl) as compared to SHRs which drink only water and show only sporadic cerebrovascular lesions. We have now assayed the incorporation of labelled choline, ethanolamine, glycerol and arachidonic acid into the phospholipids from the cortex and hippocampus of SHR-water and SHR-NaCl at different time intervals from injection into the lateral ventricle of the brain. A noticeable decrease of both choline and arachidonate specific activity (SA) in the phospholipids was found in the cortex and hippocampus (where the effect is most evident) from SHR-NaCl. Based on the literature and the data obtained, we suggest that in SHR-NaCl brain areas a release of choline and fatty acid also occurs from choline glycerophospholipids as a consequence of the cerebrovascular lesions caused by NaCl treatment. Even if a relatively minor loss of the amount of the lipids studied is evident from our results as compared to their entire pool, this change may be quite important if it causes a modification of the lipidic bilayer in excitable membranes. In a parallel group of SHR-NaCl animals, treated with the nootropic drug oxiracetam, we observed that the metabolic utilization of the precursors was completely restored. These experimental data favour the hypothesis that oxiracetam is effective in stimulating the phospholipid metabolism rate at levels even higher than those of the SHR-water animals.

Animals↗
PubMedDate not supplied

Linoleic acid metabolism in brain cortex of aged rats.

The linoleic acid metabolism was examined in the brain cortex of 4 month-old and 24 month-old rats. After the injection of [1-14C]-linoleate into the lateral ventricle of the brain the animals were sacrificed at 1,3 and 6 hours from the injection. The linoleate (18:2) incorporation into lipids, the presence of fatty acid peroxidation products, as well as the 18:2 transformation into elongated and desaturated derivatives were determined. Both an age-related reduction in linoleate incorporation rate into glycerophospholipids and a decrease in fatty acid turnover were found. Furthermore, in glycerophospholipids from 24 month-old rat brain cortex a higher level of hydroperoxide derivative of linoleate was found as compared to 4 month-old animals, and this damaged fatty acid is eliminated more slowly in aged rats than in adults. Finally, unlike 4 month-old animals, a stimulation of the transformation rate of linoleate into desaturation (6,9,12-C18:3) and elongation (8,11,14,C20:3) products was found in 24 month-old rat brain cortex. On the contrary, as far as arachidonic acid (one of the most important end products of the mechanism of linoleate modification) is concerned, the differences between aged and control animals were small, making it quite difficult to attribute a physiological meaning to this phenomenon.

Aging↗