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Biomedical subjects

G Toffano

Publications and source records attributed to G Toffano.

At least 127 records · Page 7Linked to original sources
PubMed1983

Gangliosides increase the survival of lesioned nigral dopamine neurons and favour the recovery of dopaminergic synaptic function in striatum of rats by collateral sprouting.

The effects of chronic ganglioside treatment GM-1 (10 mg/kg, i.p., once daily for 56 days) have been evaluated on the degenerative and regenerative features of nigrostriatal dopamine (DA) neurons following a partial lesion by tyrosine hydroxylase immunocytochemistry in combination with morphometrical analysis and by quantitative DA receptor autoradiography. Chronic GM-1 treatment resulted in the maintenance in the number of DA cell bodies, terminals and striatal area on the lesioned side and also increased dendrite length of the DA nerve cells in the zona reticulata on that side. The lesion induced DA receptor supersensitivity was counteracted by chronic treatment with GM-1 and the apomorphine induced rotational behaviour was significantly reduced. The hypothesis is introduced that following ganglioside treatment some lesioned DA nerve cells do not degenerate, but elongate their dendrites to give increased trophic support to DA cell bodies with intact DA axons. These increased dendro-dendritic interactions may enable the unlesioned DA cells to increase the density of their striatal nerve terminal networks via collateral sprouting leading to recovery of dopaminergic synaptic function as evidenced in the receptor autoradiographical and behavioural analysis. Gangliosides may therefore possibly represent a new type of drug in the treatment of Parkinson's disease and aging processes in DA systems.

Animals↗
PubMed1982

Age-related changes of benzodiazepine and GABA binding sites in the rat retina.

The changes in the number and sensitivity of benzodiazepine and GABA binding sites in the rat retina during postnatal development, adulthood and ageing and their functional relationship at different ages have been studied. Data indicate an increase in the total number of both GABA and benzodiazepine binding sites with age. In contrast, the activation of retinal benzodiazepine receptor binding by GABA is significantly reduced in aged rats with respect to young adult and newborn rats. Moreover, the activation of retinal benzodiazepine receptor binding induced by dark exposure of the animals is present in young adult rats but is lost in aged rats. These results suggest that in the retina of aged rats there is an increase of GABA and benzodiazepine receptors which have lost their functional connection.

Aging↗
PubMed1982

Changes with age in rat central monoaminergic system responses to cold stress.

Changes with age in responses to stress of certain central monoaminergic systems were investigated. Three groups of rats, 4, 18 and 29 months old, were exposed to cold and the effect of this stress on hypothalamic tyrosine hydroxylase, and on the metabolism of DA and 5HT in different brain regions was evaluated. Senescent rats were unable for several hours to compensate the loss of body heat. Corticosterone secretion however was equally stimulated. Hypothalamic tyrosine hydroxylase activity was enhanced in the young rats but not in the old ones. However, the two groups of senescent rats did not show the increase in HVA levels noted in striata of young rats 2 hours after cold exposure. In contrast, the 18 and 29-month-old rats presented enhanced serotonergic tonus, indicated by the greater increase in 5HIAA determined by stress.

Aging↗
PubMed1982

Changes in monoamines and their metabolite levels in some brain regions of aged rats.

The concentrations of dopamine (DA) norepinephrine (NE), serotonin (5HT) and their metabolites, HVA, DOPAC, MHPG-SO4 and 5HIAA were measured in several brain areas of rats aged 4, 18 and 29 months. Dopamine and its metabolites showed a decline, statistically correlated with age, in all the dopaminergic areas considered, indicating that this system is profoundly affected in the senescent rat. The changes in the noradrenergic system were more complex. This neurotransmitter was reduced in spinal cord and in limbic area, but was not modified in hippocampus, cerebellum, striatum and s. nigra. In cortex, MHPG-SO4, the main NE metabolite, showed a significantly age-related increase. Tyrosine hydroxylase (TH) activity was low in striatum, and brainstem but not in hypothalamus of aged rats. Neither 5HT nor its metabolites was affected by age. The results indicate that central catecholaminergic systems are markedly affected in senescent rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Age dependent changes in the methylation of rat brain phospholipids.

Phospholipid methyltransferase I and II enzymes methylate phosphatidylethanolamine three times to form phosphatidylcholine. The activity of these two enzymes was determined in synaptosome-enriched fractions from rats 1, 3, 7, 15 and 21 months old. The activity of phospholipid methyltransferase I was significantly greater in 7-, 15- and 21-month-old rats than in 1- and 3-month-old rats. In contrast, the activity of phospholipid methyltransferase II did not change with age. These changes in methyltransferase activity with increasing age may be related to changes in beta-receptor function with increasing age.

Aging↗
PubMed1981

Regulation of GABA receptor binding to synaptic plasma membrane of rat cerebral cortex: the role of endogenous phospholipids.

Triton X-100 treatments produced an extensive depletion of proteins and phospholipids and a marked increase of [3H] GABA binding on synaptic plasma membranes (SPM). Maximal [3H]GABA binding was obtained with three Triton X-100 treatments (+ 174% with respect to control). Phospholipase C, which removes only the phospholipid polar head, induces a 40% increase of [3H]GABA binding only after treatments resulting in extensive protein depletion. In reconstitution experiments phosphatidylethanolamine, the largest phospholipid removed, induced a 30-35% inhibition of [3H]GABA binding in Triton X-100 treated membranes; in contrast phosphatidylserine and phosphatidylcholine did not produce significant changes. The reconstitution of phospholipase C-treated SPM preparations with exogenous phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine or phosphoethanolamine and 1,2-dipalmitoylglycerol, products of phospholipase C activity, did not yield significant changes. This evidence, which argues against a direct role of phospholipids on the regulation of GABA binding, should, however, suggest that the GABA binding component of the receptor site is a lipoprotein or a lipid-depending protein.

Animals↗
PubMed1981

Functional interaction between benzodiazepine and GABA recognition sites in aged rats.

The present study was undertaken to explore whether there may be age-related changes in benzodiazepine binding and in the functional interaction between GABA and benzodiazepine recognition sites. Data indicate an increase in benzodiazepine binding sites with age. Moreover the functional interactions between GABA and benzodiazepine receptor sites are differentially affected by aging. GABA is less active in enhancing benzodiazepine binding in the older animals because of the loss of GABA receptors, and Diazepam may be more active in enhancing GABA receptor binding in the aged animals because there are more benzodiazepine receptors in this group. An understanding of the relevance of the apparent alteration in coupling between GABA and benzodiazepine receptors must permit a better definition of the behavioral manifestation of their biochemical phenomenon.

Aging↗
PubMed1981

Activation of (Na+, K+)-ATPase by nanomolar concentrations of GM1 ganglioside.

GM1 ganglioside binding to the crude mitochondrial fraction of rat brain and its effect on (Na+, K+)-ATPase were studied, the following results being obtained: (a) the binding process followed a biphasic kinetics with a break at 50 nM-GM1; GM1 at concentrations below the break was stably associated, while over the break it was loosely associated; (b) stably bound GM1 activated (Na+, K+)-ATPase up to a maximum of 43%; (c) the activation was dependent upon the amount of bound GM1 and was highest at the critical concentration of 20 pmol bound GM1 X mg protein-1; (d) loosely bound GM1 suppressed the activating effect on (Na+, K+)-ATPase elicited by firmly bound GM1; (e) GM1-activated (Na+, K+)-ATPase had the same pH optimum and apparent Km (for ATP) as normal (Na+, K+)-ATPase but a greater apparent Vmax; (f) under identical binding conditions (2 h, 37 degrees C, with 40 nM substance) all tested gangliosides (GM1, GD1a, GD1b, GT1b) activated (Na+, K+)-ATPase (from 26-43%); NeuNAc, sodium dodecylsulphate, sulphatide and cerebroside had only a very slight effect. It is suggested that the ganglioside activation of (Na+-K+)-ATPase is a specific phenomenon not related to the amphiphilic and ionic properties of gangliosides, but due to modifications of the membrane lipid environment surrounding the enzyme.

Animals↗
PubMed1981

Ontogeny of 3H-diazepam binding sites in different rat brain area. Effect of GABA.

The ontogenesis of the 3H-diazepam binding sites and their modulation by gamma-aminobutyric acid have been studied in different brain areas of rat at various ages, using frozen and two Triton X-100 treated crude synaptic membrane preparations. Benzodiazepine recognition sites are present at birth in all the brain regions investigated and reach adult levels about 3 weeks later. The changes of 3H-diazepam binding with age are due to an increase in the total number of binding sites. In vitro addition of GABA produces, in newborn and adult cerebral cortex, an increase in affinity, but not in number of binding sites for 3H-diazepam. The effect is age dependent.

Aging↗
PubMed1981

In vivo and in vitro interference of phosphatidylserine liposomes on prolactin secretion in the rat.

The effect of sonicated suspensions of phosphatidylserine (PS), an acidic phospholipid, was investigated on prolactin secretion utilizing in vivo and in vitro approaches. Acute and chronic administration of PS reduced plasma prolactin levels during different phases of circadian rhythms. The phospholipid was able to inhibit the plasma prolactin surge, which occurs in cycling female rats on the afternoon of proestrus. The time course of PS on prolactin secretion was characterized by a short latency (15 min) and a long duration of action (6 h). In rats with hypothalamic deafferentation PS partially reduced the increase of circulating prolactin induced by pretreatment with alpha-methyltyrosine. An inhibition of prolactin release was observed if anterior pituitary glands were incubated in presence of PS. This effect was prevented by the addition of the dopamine antagonist sulpiride to the medium. In conclusion, PS decreases prolactin secretion both in vivo and in vitro. The inhibition of the hormone secretion appears to be due to the action of PS at the level of the pituitary; however, a concomitant stimulatory action on the turnover of the tuberoinfundibular neurons cannot be ruled out.

Animals↗