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Biomedical subjects

G Toffano

Publications and source records attributed to G Toffano.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Phosphatidylserine-induced modulation of the immune response in mice: effect of intravenous administration.

The action of phosphatidylserine on the immune response has been examined in mice after the intravenous administration of phospholipid or exposing cultured splenocytes to the action of phosphatidylserine vesicles. Phosphatidylserine (5-25 mg/kg) reduces the T-dependent and the T-independent antibody production. This effect is observed when the phospholipid is injected before (4 h) but not after (24 h) the immunization. The decreased influence of phosphatidylserine injected 24 h before the immunization indicates the reversibility of the action of phospholipid. The effect on the immune system may in part reflect a direct interaction with lymphocytes, since phosphatidylserine (12-60 microM) decreases the production of T-cell growth factors (mainly interleukin-2) elicited by mitogens in cultured spleen cells and reduces the expression of growth factor receptors in the same cells activated by mitogens. In addition, the activity of T-helper cells is found to be reduced in mice receiving the injection of phosphatidylserine. By contrast, the antigen processing and presentation by macrophages is not affected. The data suggest that the intravenous injection of phosphatidylserine vesicles in mice is followed by a transient decrease of lymphocyte activity.

Animals↗
PubMedDate not supplied

Age-dependent spontaneous EEG bursts in rats: effects of brain phosphatidylserine.

During aging, male Sprague-Dawley rats display increasing frequency of bursts of seizure-like EEG patterns. They also have a decreased retention of passive avoidance response and a loss of spontaneous alternation in a Y maze. A study was made on the effects of chronic administration of phosphatidylserine in aged rats. It was found that BC-PS reduced by 65% the number of seizures, and by 70% their duration. It also facilitated retention of passive avoidance and of spontaneous alteration behavior. These results suggest that phosphatidylserine can affect electrophysiological and behavioral parameters in aged rats probably by counteracting age-related biochemical changes.

Aging↗
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D-1 dopamine receptors labelled with 3H-SCH 23390: decrease in the striatum of aged rats.

The effects of age on the binding parameters of 3H-SCH 23390, the most selective D-1 dopamine receptor ligand available at present, were studied in membrane preparations from rat striatum. When compared with 3 month old animals, there was a significant decrease in the density of 3H-SCH 23390 binding sites in 20 month old (-37%) and in 26 month old (-44%) rats, without alterations in the apparent dissociation constant values. No significant changes in the density or affinity of D-1 DA receptors were observed in 14 month old rats. In view of the behavioural effects mediated by D-1 DA receptors recently described (i.e., grooming, stereotypies and EEG desynchronization), the decrease in the density of these receptors in senescent rats may underlie some of the age-related alterations in dopaminergic functions in the rat brain.

Aging↗
PubMedDate not supplied

Age-related changes in metabolic responses to chronic monoamine depletion in central dopaminergic and serotonergic systems of rats treated with reserpine.

Groups of 5, 15, and 27-month-old rats were treated with reserpine (5 mg/kg IP) and killed after 1, 7, 14, and 21 days. Reserpine's effects on dopamine (DA) and serotonin (5HT) metabolism were studied in the striata and limbic areas, on the basis of changes in metabolite concentrations and a calculated index [delta(C/M)] expressing changes in the molar ratio between metabolite and parent monoamine. Twenty-four hours after drug treatment, when the two monoamines reached a new steady-state, about 10% of the normal concentration, there was evident enhancement in the metabolism of striatal DA, indicated by HVA levels and delta(C/M) changes. This increase was significantly lower in the senescent rats. In contrast with HVA, the levels of DOPAC were lowered in reserpinized rats. This effect, present in all three age groups, lasted up to 21 days in young and 14 days in adult and old rats. However, for this metabolite too, the delta(C/M) indicated an increase in its formation which was lower in 27-month-old rats. Similar effects were observed in limbic areas, but here the age-related differences were less evident. Serotonin metabolism was also increased by reserpine as indicated by the delta(C/M). This parameter was lower in young than in adult and old rats, at least in limbic area. Similarly, 5HIAA increased only in the senescent rats. These age-related differences were not evident in striata. In this rat population, aging apparently modified the compensatory metabolic responses of some dopaminergic and serotonergic systems. The direction of these changes, however, depends on the system and the brain region considered.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Dendritic spine loss in hippocampus of aged rats. Effect of brain phosphatidylserine administration.

Dendritic spine density of pyramidal cells in region CA1 of the hippocampus has been evaluated in young (3 months), old (27 months) and old phosphatidylserine (BC-PS)-treated rats. BC-PS (50 mg/kg, suspended in tap water) was administered daily, starting at the age of 3 months until 27 months. Spine density was analyzed on Golgi-stained pyramidal neurons by a computerized analysis system. In 27-month-old rats, spine density showed with respect to 3-month-old animals, a significant decrease in both basal and apical dendrites (p less than 0.01; one-way ANOVA), with a mean loss of 12.11% in the basal dendrites and of 10.64% in the apical ones. In 27-month-old rats treated with BC-PS, values of spine density were not statistically different when compared to those of 3-month-old animals. The mechanisms underlying the beneficial effect of BC-PS treatment on neuronal connectivity might be explained on the basis of its pharmacological actions on neuronal membranes [9], neurotransmission [43] and/or interaction with NGF [7].

Aging↗
PubMedDate not supplied

Failure of dark adaptation to upregulate D-1 dopamine receptors in retina of senescent rats.

The effect of aging on the binding parameters of 3H-SCH 23390, the most selective ligand of D-1 DA receptors, was studied in membrane preparations from the rat retina. DA-stimulated adenylate cyclase activity was also measured in order to better characterize the changes in retinal D-1 DA receptors induced by aging. The binding studies revealed that the density of 3H-SCH 23390 was increased (34 and 73%) in the retina of 14- and 26-month-old rats, when compared to young adult animals, respectively. In contrast, aging failed to alter the sensitivity of the adenylate cyclase to the action of DA. In fact, DA (10(-6) M to 10(-4) M) elicited a similar enhancement in cyclic AMP formation in retinal homogenates of both adult and senescent rats. Since dark adaptation increases the density of D-1 DA receptors in the retina of adult rats we studied the effect of light deprivation on 3H-SCH 23390 binding and DA-sensitive adenylate cyclase activity in the retina of senescent rats. As previously shown (25) light deprivation increased 3H-SCH 23390 binding and enhanced DA-sensitive adenylate cyclase activity in the retina of young adult rats. On the contrary, dark adaptation failed to increase 3H-SCH 23390 binding and to enhance DA-sensitive adenylate cyclase activity in the retina of senescent rats. Taken together these results indicate that D-1 DA receptors in the retina of aged rats have biochemical and functional properties different from those found in the retina of adult animals; these changes may result in an altered response to the physiological stimuli elicited by environmental lighting.

Adenylyl Cyclases↗
PubMedDate not supplied

Neurochemical alterations but not nerve cell loss in aged rat neostriatum.

Numerical changes in the overall neostriatal neuronal population have been investigated by morphometric analysis of Nissl-stained and glucocorticoid receptor-immunoreactive neurons. Number and staining intensity of various chemically-identified nerve cell populations were analysed by means of immunocytochemistry coupled with computer-assisted image analysis. Three- and 24-month-old male Sprague-Dawley rats were used. No change in the number of Nissl-stained, glucocorticoid receptor-, dopamine and adenosine 3':5'-monophosphate-regulated phosphoprotein- and enkephalin-immunoreactive neurons and a 50% decrease of neuropeptide Y-immunoreactive neurons were observed in the aged rat. In our preparations, the glucocorticoid receptor antibody stains around 90% of the neostriatal neurons, the dopamine and adenosine 3':5'-monophosphate-regulated phosphoprotein and enkephalin antibodies label 25-35% and the neuropeptide Y antibody stains only 1% of neostriatal neurons. In the same preparations a significant decrease in the intensity of immunostaining was observed for enkephalin-, dopamine and adenosine 3':5'-monophosphate-regulated phosphoprotein- and neuropeptide Y-immunoreactive neuronal cell bodies and tyrosine hydroxylase-immunoreactive nerve terminals in the aged rat. In the case of neuropeptide Y- and dopamine and adenosine 3':5'-monophosphate-regulated phosphoprotein-immunoreactive neurons, the changes in the intensity of immunostaining were differentially compartmentalized within neostriatum, suggesting selective vulnerability of striatal subregions to ageing processes. In conclusion, these data indicate that no significant age-related neuronal cell loss occurs in neostriatum. On the other hand, a generalized decrease in the levels of peptide transmitters and molecules related to dopamine transmission is observed in aged rat neostriatum, possibly resulting in the known age-related deficits of neostriatally-controlled behaviours.

Aging↗
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Differential response to immobilization stress of striatal dopaminergic and hippocampal noradrenergic systems in aged rats.

The effect of restraint stress on synthesis of central norepinephrine (NE) and dopamine (DA) was studied in adult and old rats. The rate of in vivo synthesis of the two catecholamines was determined in hippocampus (a prevalently noradrenergic area) and in striatum (a prevalently dopaminergic area) by measuring the accumulation of DOPA for 60 min after decarboxylase inhibition. NE synthesis was stimulated by stress in the first 30 min, after which the accumulation of DOPA declined. The stimulation was much greater in old rats. In striatum, endogenous DOPA concentration was significantly lower in old rats. Stress significantly enhanced DOPA accumulation in the first 30 min in both age groups but after this interval accumulation continued linearly only in young rats. These results indicate that in aged rats the response to stress of some noradrenergic and dopaminergic systems may be altered in opposite directions.

Aging↗
PubMedDate not supplied

Evaluation of tuberoinfundibular dopamine function by neuropharmacologic means in old male rats.

Baseline prolactin (PRL) levels and the PRL-lowering effect of nomifensine (Nom), an indirect dopamine (DA) agonist, were evaluated in young adult (3-5 months) and old (21 and 27 months) male rats. In addition, PRL responsiveness to acute or repeated administration of haloperidol (Hal), a DA receptor antagonist, was assessed in either young or old rats. Baseline PRL levels did not differ significantly between young and aged rats either when rats were killed by decapitation or underwent sampling from the retro-orbital venous plexus. Administration of Nom (10.0 mg/kg i.p.), a drug which inhibits PRL levels in normal rats and humans but lacks any action in conditions of impaired tuberoinfundibular DA (TIDA) function, affected PRL levels in aged rats not differently than in young rats. The PRL inhibition induced by the drug was greater in both groups when basal PRL levels were higher. Acute administration of Hal (0.5 mg/kg i.p.) increased significantly and to the same extent as PRL levels in aged and young rats. In aged rats treated chronically with Hal (0.5 mg/kg i.p., twice daily for 14 days) and sampled at the 8th day, 1 h after the first daily Hal injection, plasma PRL rose to levels about 3-fold as high as those after the first injection; in young rats, instead, the PRL-releasing effect of Hal was similar to that evoked by the first administration. 3 days after Hal withdrawal, baseline PRL levels were significantly higher in aged Hal-treated rats than in vehicle-injected or young Hal-treated rats and so were pituitary concentrations of PRL.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

Effect of the ganglioside GM1, on cerebral metabolism, microcirculation, recovery kinetics of ECoG and histology, during the recovery period following focal ischemia in cats.

The effect of the ganglioside GM1 on the recovery of local cerebral glucose metabolism (lCMRgl), recovery kinetics of cerebrocortical electrical activity, cerebral blood flow and redox state as well as histological changes following focal ischemia has been studied in the cat. Ischemia was produced by occlusion of the left middle cerebral artery (MCA), and GM1 (30 mg/kg) was injected intravenously at 30 min after the MCA occlusion or at the time of release of the occlusion, at 120 min. Another group of animals were subjected to the same ischemic insult, but without GM1 treatment, and sham-operated treated and not treated cats were also studied. The animals of both GM1-treated and non-treated stroke groups were classified into 2 groups (severe and moderate) depending on the depression of electrocortical activity in the ischemic hemisphere at 30 min of the ischemia. There was a significant increase in local cerebral blood flow in the ischemic area in the treated animals. Additionally there was a significant treatment effect on the left peripheral MCA territory for lCMRgl in the 30 min treated moderate group, (p less than .05). This group of animals showed decreased lCMRgl accompanied by less severe histological damage suggesting that GM1 may produce metabolic depression so as to maintain a normal flow-metabolism couple and prevent ischemic structural damage. The possible mechanism of metabolic depression induced by GM1 is briefly discussed.

Animals↗
PubMedDate not supplied

Lysophosphatidylserine-induced activation of mast cells in mice.

Intravenous injection of lysophosphatidylserine (2.5-25 mg/kg) increases the blood histamine level in mice. Lysophosphatidyl-D-serine, alkyl-lysophosphatidylserine and glycerophosphorylserine show little or no activity. As shown by the similar efficacy of the analogue lacking the OH group in the C-2 position of glycerol conversion into phosphatidylserine is not required. The age of mice influences the activity of lysophosphatidylserine. Thus, the increase in blood histamine is greater in adult mice (8-10 weeks) than in young mice (4-6 weeks). In old mice (50-60 weeks) the tolerance to lysophosphatidylserine is reduced. Repeated parenteral administrations induce depletion of histamine stores with concomitant desensitization to lysophosphatidylserine. Well-perfused organs containing connective tissue mast cells (tongue) are more affected. When [3H] histidine is injected into lysophosphatidylserine-treated mice, the highly radioactive histamine detected in the tongue indicates the preservation of histidine decarboxylase activity after degranulation. The data suggest that lysophosphatidylserine specifically activates connective tissue mast cells in mice.

Animals↗
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TSH circadian secretions in aged men and effect of phosphatidylserine treatment.

In 20 euthyroid aged men (from 65 to 85 years of age) no significant circadian periodicity of thyrotropin (TSH) secretion has been shown by the population mean cosinor method. At the end of a period of 30 days of hospitalization the cosinor evaluation of TSH secretion showed a restored highly significant (p less than 0.001) circadian rhythmicity in phosphatidylserine (PS) (400 mg/daily) treated group (10 aged subjects). By contrast, hospitalization seems to further deteriorate the periodicity of the hormone secretion in 10 placebo-treated subjects.

Aged↗