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Biomedical subjects

G Vantini

Publications and source records attributed to G Vantini.

At least 37 records · Page 2Linked to original sources
PubMed1991

Nerve growth factor differentially modulates the expression of its receptor within the CNS.

The effect of nerve growth factor on the expression of nerve growth factor receptor in the central nervous system of newborn and adult rats was studied by means of immunohistochemistry with the monoclonal antibody 192-IgG. Both during development and in adulthood, the intracerebroventricular administration of nerve growth factor elicited a pronounced increase of nerve growth factor receptor-like immunoreactivity in the cell bodies and neural processes of the basal forebrain cholinergic nuclei, as compared to cytochrome c-treated rats (controls). A pronounced nerve growth factor-induced increase of nerve growth factor receptor-like immunoreactivity was also observed in central regions innervated by trigeminal and spinal ganglia. A moderate to a marked increase of nerve growth factor receptor-like immunoreactivity was evident in some mesencephalic visual system-related structures and thalamic nuclei expressing nerve growth factor receptor. In contrast, NGF treatment did not induce appreciable modification of nerve growth factor receptor-like immunoreactivity in cerebellar, brainstem, and spinal motor structures of newborn rats. In adult nerve growth factor-treated rats, a decrease of nerve growth factor receptor-like immunoreactivity was detected in the cerebellum, whereas no re-expression of nerve growth factor receptor-like immunoreactivity occurred in the motor structures that had expressed it in the first postnatal week. Finally, nerve growth factor was also found to enhance, in both adult and newborn rats, nerve growth factor receptor-like immunoreactivity associated with ependymal and subependymal cellular elements of the lateral and third ventricles, as well as with the leptomeninges overlying the superior colliculus and supraoptic area. The present results indicate that endogenous nerve growth factor or nerve growth factor-like molecules may play a dynamic role in a variety of cell populations of both the developing and mature mammalian central nervous system. We thus propose the nerve growth factor ability to modulate its receptor in vivo as a novel criterion to define nerve growth factor or nerve growth factor-like molecules, sensitive neuronal, and non-neuronal cells. Whereas this criterion does not intrinsically possess absolute physiological validity, its pharmacological concomitants might be relevant in view of the proposed therapeutical use of this trophic factor.

Aging↗
PubMed1991

Nerve growth factor prevents the amblyopic effects of monocular deprivation.

Monocular deprivation early in life causes dramatic changes in the functional organization of mammalian visual cortex and severe reduction in visual acuity and contrast sensitivity of the deprived eye. We tested whether or not these changes could be from competition between the afferents from the two eyes for a target-derived neurotrophic factor. Rats monocularly deprived during early postnatal development were treated with repetitive intraventricular injections or topical administration of nerve growth factor. The effects of monocular deprivation were then assessed electrophysiologically. In untreated animals visual acuity and contrast sensitivity of the deprived eye were strongly reduced, whereas in nerve growth factor-treated animals these parameters were normal.

Amblyopia↗
PubMed1991

Choline acetyltransferase messenger RNA expression in developing and adult rat brain: regulation by nerve growth factor.

The polymerase chain reaction (PCR) was used to develop a method for detection and relative quantification of the choline acetyltransferase (ChAT) mRNA in neonatal and adult rat CNS. Oligonucleotide primers derived from a porcine ChAT cDNA sequence were used in coupled reverse transcriptase (RT)-PCR to amplify a cDNA sequence of 206 bp which arises in a cycle- and RNA-dependent manner and which hybridizes with both an internal oligonucleotide and a ChAT cDNA probe. ChAT mRNA was detected in spinal cord, septal area, striatum, cortex and hippocampus but not in cerebellum and cardiac or skeletal muscle. In the septal area, relative quantitative evaluation of ChAT mRNA levels by RT-PCR indicates that this transcript is developmentally regulated and increased following intracerebral administration of nerve growth factor (NGF) to both neonatal and young adult rats. This suggests that the increases of ChAT activity observed in basal forebrain during development or after NGF administration are, at least in part, associated with an increase in corresponding levels of mRNA.

Aging↗
PubMed1990

Nerve growth factor induces a dose-dependent and long-lasting increase of choline acetyltransferase activity in the septal area and hippocampus of uninjured rats.

The effect of nerve growth factor (NGF) on the intact septohippocampal cholinergic system of adult rats was studied. Nerve growth factor was continuously infused at different doses (5-100 micrograms) for two weeks into the lateral ventricle of adult rats. Controls received intracerebroventricular infusion of equal amounts of cytochrome c. Nerve growth factor treatment was capable of inducing a dose-dependent increase of choline acetyltransferase activity (ChAT) in septal area and ventral hippocampus. In both areas, the NGF-induced rise of ChAT activity was sustained for at least one week after infusion, then it progressively declined towards control values. By three and five weeks, using NGF at 25 and 100 micrograms respectively, ChAT increase was still significant in both septum and ventral hippocampus. The present findings corroborate a role for NGF in adult septohippocampal cholinergic system and indicate that the "pharmacological" modulation of these neurons by NGF may last several weeks following withdrawal of this trophic factor.

Animals↗
PubMed1989

Nerve growth factor affects uninjured, adult rat septohippocampal cholinergic neurons.

The effect of nerve growth factor on the intact versus injured septohippocampal cholinergic system of adult rats was studied. Nerve growth factor was continuously infused into the lateral ventricle of adult uninjured rats or rats that had received unilateral partial transection of the fimbria. Controls (operated and unoperated) received intraventricular infusion of cytochrome c. After 2 weeks of nerve growth factor or cytochrome c treatments, choline acetyltransferase and acetylcholinesterase activities were measured in the septal area and in the hippocampus (divided into dorsal, medial and ventral parts). The continuous infusion of nerve growth factor resulted in a marked dose-dependent increase of choline acetyltransferase activity in both septum and hippocampus of adult unlesioned rats. In lesioned rats the nerve growth factor treatment was capable of inducing choline acetyltransferase activity in the hippocampus of not only the lesioned but also the unlesioned side, as well as in the septal area. In addition, nerve growth factor affected choline acetyltransferase activity differently in the hippocampus of the operated side with respect to the contralateral side or in unoperated animals. The chronic infusion of nerve growth factor did not affect acetylcholinesterase activity in the septum or in the hippocampus of either lesioned or unlesioned rats. The present findings indicate that nerve growth factor is capable of modulating the function of not only damaged but also normal adult forebrain cholinergic neurons. This suggests that nerve growth factor may modulate the function of these neurons in adulthood.

Acetylcholinesterase↗
PubMed1989

Evidence for a physiological role of nerve growth factor in the central nervous system of neonatal rats.

Forebrain cholinergic neurons have been shown to respond in vivo to administration of nerve growth factor (NGF) with a prominent and selective increase of choline acetyltransferase (ChAT) activity. This has suggested that NGF can act as a trophic factor for these neurons. To test this hypothesis directly, anti-NGF antibodies (and their Fab fragments) were intracerebroventricularly injected into neonatal rats to neutralize endogenously occurring NGF. The anti-NGF antibody administration produced a decrease of ChAT activity in the hippocampus, septal area, cortex, and striatum of rat pups. This finding was substantiated by a concomitant decrease of immunopositive staining for ChAT in the septal area. These effects indicate that the occurrence of endogenous NGF in the CNS is physiologically relevant for regulating the function of forebrain cholinergic neurons.

Animals↗
PubMed1988

GM1 ganglioside potentiates the effect of nerve growth factor in preventing vinblastine-induced sympathectomy in newborn rats.

The effects of vinblastine (VNB) and nerve growth factor (NGF) administrations were assessed on sympathetic nerve terminals by measuring the noradrenaline (NA) content in the heart, spleen and kidneys of developing animals. Six-day-old rats, treated with 0.15 mg/kg VNB on postnatal day 3 (P3) showed a dramatic decrease of NA content in all these organs. This reduction was prevented by daily administrations of NGF on P3, P4 and P5. The effectiveness of NGF in inhibiting the VNB-induced sympathectomy was related to the dose administered and to the time interval between the VNB administration and the first NGF injection given on P3. Dose-response curves to NGF (ranging from 0.01 to 0.5 mg/kg) were obtained in both heart and spleen of VNB-treated animals. Thus, this experimental paradigm provides a quantitative assessment of the NGF activity in vivo. The systemic administration of GM1 (30 mg/kg) on P3, P4 and P5, was able to potentiate the NGF activity in preventing the VNB-induced sympathectomy. This GM1 effect was more evident in the heart and may be, at least in part, attributed to increased NGF prevention of neuronal cell death due to VNB. These results suggest an in vivo interaction between exogenous GM1 and NGF and are consistent with the view that neuronal cell repair related to in vivo administration of this ganglioside may rely on its capability to modulate the activity of endogenously occurring neuronotrophic factors.

Adrenergic Fibers↗
PubMed1986

Effects of sustained hyperprolactinemia induced by chronic treatment with domperidone on central dopaminergic systems in the rat.

Chronic treatment with Domperidone (DOM) had no effect on basal prolactin (PRL) secretion or basal levels of Dopamine (DA) metabolites in basal hypothalamus and striatum as compared with the vehicle treated rats. Animals chronically treated with DOM did not present tolerance to a challenge dose of Haloperidol (HAL) and DOM either measuring PRL secretion or striatal DA metabolite levels. The PRL-induced increase in hypothalamic 3,4-dihydroxyphenylacetic acid (DOPAC) was reduced. These results were accompanied by no change at striatal DA receptors, a slight reduction in density-affinity at hypothalamic DA receptors but clear-cut modification in pituitary DA receptors with the appearance of a high affinity-low capacity binding sites. It can be surmised that sustained hyperprolactinemia may induce tolerance in hypothalamic Tuberoinfundibular (TIDA) neurons involved in the inhibitory control of PRL secretion and a change in the kinetic properties of pituitary DA receptors, but it does not consistently affect the activity of the nigro-striatal DA system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

In vivo and in vitro evidence of dopaminergic system down regulation induced by chronic L-DOPA.

The biochemical modifications which occur in the dopaminergic system after chronic administration of L-DOPA are investigated. Levels of DA and of its metabolite 3-methoxytyramine (3-MT), an expression of the amount of DA released, were raised to the same extent in controls given a single dose of 1-DOPA and in chronically treated rats given 100 mg/kg of 1-DOPA plus 25 mg/kg of benserazide twice a day for 24 days. However, the reduction in neuronal function expressed by the decrease in 3-MT which follows treatment with DA agonists such as piribedil and apomorphine was less pronounced in the chronically L-DOPA treated rats. This suggests that such treatment causes a down regulation of DA receptors. These in vivo results were confirmed by in vitro analysis of DA receptor activity after chronic L-DOPA. Under these conditions there was a significant reduction in the number of [3H]-spiperone and [3H]-ADTN binding sites with no changes in their affinity. The in vivo and in vitro findings both suggest the involvement of a subsensitive compensatory mechanism or down regulation of dopaminergic neurons after chronic treatment with L-DOPA.

Animals↗
PubMed1984

Age-related modification of dopaminergic and beta-Adrenergic receptor system: restoration to normal activity by modifying membrane fluidity with S-adenosylmethionine.

Microviscosity of membranes prepared from striata and cortex of 3 or 30-month-old rats was measured by fluorescence polarization and electron spin resonance. The viscosity of the hydrophobic core of the lipid bilayer was significantly increased in striatal but not in cortical membranes of old rats. In old rats the incorporation of methyl groups into phosphatidylcholine was significantly lower than in young rats. beta-Adrenergic specific binding sites were reduced in striata, cortex and pineal gland of old rats. In the striata of these animals, [3H] spiperone specific binding sites and dopamine-stimulated adenylate cyclase were also low. A chronic treatment of old rats with S-adenosyl-L-methionine, the cofactor in phospholipid methylation, lowered microviscosity to normal values in striata but not in the cortex. In the same old rats, the beta-receptor in striata and pineal gland returned towards juvenile values; in the cortex, the modification was in the same direction but did not reach significance. Neither putative dopaminergic receptors nor the adenylate cyclase age-dependent decrease was modified by treatment with S-adenosyl-L-methionine.

Aging↗
PubMed1984

Brain epinephrine systems: detailed comparison of adrenergic and noradrenergic metabolism, receptor number and in vitro regulation, in two inbred rat strains.

Epinephrine content and PNMT activity in medulla pons and hypothalamus of F344 inbred rats is from 3- to 8-fold higher than that of Buf inbred rats. These strain-dependent differences in brain adrenergic neurons are reciprocally related to altered alpha 1- adn alpha 2-adrenergic receptor density in PNMT-containing brain regions. Radioligand binding indices related to alpha 2-receptor function reveal that receptors may be 'desensitized' as well as 'down-regulated' in the strain with high PNMT activity (F344), and may be 'supersensitive' as well as 'up-regulated' in the strain with low PNMT activity (Buf). The association between epinephrine-containing neurons and alpha-adrenergic receptor regulation appears specific, since alpha-adrenergic receptor density and regulation in brain regions devoid of PNMT and epinephrine is similar in F344 and Buf rats. While noradrenergic metabolism in F344 rats is greater than that in Buf rats, this difference is generalized throughout the brain and, thus, bears no apparent relationship to the localized alterations in alpha-adrenergic receptor density. Moreover, beta-adrenergic receptor density in the 2 strains is similar in all brain regions. These data suggest that a significant proportion of alpha-adrenergic receptors in medulla-pons and hypothalamus are intimately related to and regulated by epinephrine-containing nerve endings.

Animals↗
PubMed1984

Phencyclidine-induced locomotor activity in the rat is blocked by 6-hydroxydopamine lesion of the nucleus accumbens: comparisons to other psychomotor stimulants.

The present study was primarily designed to explore the relationship between phencyclidine(PCP)-induced hyperactivity and the mesolimbic dopamine (DA) system. In addition, the motor-activating and behavioral effects of amphetamine (1.5 mg/kg), SKF-10,047 (25.0 mg/kg), scopolamine (1.0 mg/kg), and caffeine (10.0 mg/kg) were also measured and compared to PCP action. While all compounds produced a moderate to large degree of hyperactivity with varying time courses for effect, gross behavioral observations indicated a greater similarity between PCP and SKF-10,047 than between any of the other drugs. Following bilateral 6-hydroxydopamine lesions of the nucleus accumbens the robust locomotor-stimulating action of 5 mg/kg PCP was significantly reduced. Such lesions also successfully prevented amphetamine- and SKF-10,047-induced hyperactivity, but not the behavioral activation produced by scopolamine or caffeine. These results suggest that PCP and SKF-10,047, like amphetamine, elicit locomotor activity through presynaptic DA mechanisms within the mesolimbic system.

Animals↗
PubMed1984

Inheritance of adrenal phenylethanolamine N-methyltransferase activity in the rat.

Phenylethanolamine N-methyltransferase (PNMT) is the enzyme that catalyzes the S-adenosyl-L-methionine-dependent methylation of (-)norepinephrine to (-)epinephrine in the adrenal medulla. Adrenal PNMT activity is markedly different in two highly inbred rat strains; enzyme activity in the F344 strain is more than fivefold greater than that in the Buf strain. Initial characterization of the enzyme in the two inbred strains reveals evidence for catalytic and structural differences, as reflected in dissimilar Km values for the cosubstrate (S-adenosyl-L-methionine) and prominent differences in thermal inactivation curves. To assess adrenal PNMT activity in an F344 X Buf pedigree, we employed a statistical procedure to test for one- and two-locus hypotheses in the presence of within-class correlations due to cage or litter effects. The PNMT data in the pedigree are best accounted for by segregation at a simple major locus superimposed upon a polygenic background; data obtained from the biochemical studies suggest that the major locus is a structural gene locus.

Adrenal Medulla↗
PubMed1984

Assessment of the functional role of brain adrenergic neurons: chronic effects of phenylethanolamine N-methyltransferase inhibitors and alpha adrenergic receptor antagonists on brain norepinephrine metabolism.

The potential role of brain adrenergic neurons in regulating noradrenergic neuronal metabolism was assessed using inhibitors of phenylethanolamine N-methyltransferase (PNMT), the enzyme responsible for epinephrine production. Two centrally active PNMT inhibitors (SK&F 64139 and LY134046) were administered over a 6-day treatment period to cause prolonged reductions in epinephrine formation. In brain regions containing endogenous epinephrine (medulla-pons and hypothalamus), chronic treatment with PNMT inhibitors produced: 1) reductions of epinephrine content, 2) elevation of tyrosine hydroxylase activity and 3) elevation of alpha-1 and particularly alpha-2 adrenergic receptor radioligand binding sites; neither norepinephrine turnover nor beta adrenergic receptor binding was affected. In brain regions devoid of endogenous epinephrine (cerebellum, frontal cortex and hippocampus), chronic treatment with PNMT inhibitors produced 1) a variable increase in tyrosine hydroxylase activity (cerebellum only) and 2) a reduction in norepinephrine turnover; neither alpha or beta adrenergic receptor binding was altered. A PNMT inhibitor failing to cross the blood-brain barrier, SK&F 29661, and an alpha-1 adrenoceptor antagonist, prazosin, had no effect on brain catecholamine metabolism. High doses of an alpha-2 adrenoceptor antagonist, yohimbine, increased medulla-pons tyrosine hydroxylase activity but also resulted in prominent reductions in norepinephrine content in all brain regions. The results suggest that prolonged reductions in endogenous brain epinephrine formation produce unique effects on brain norepinephrine function; these effects are regionally distinctive and are qualitatively different from the effects seen with chronic alpha-1 or alpha-2 adrenergic receptor blockade. These data are consistent with regulation of brainstem norepinephrine-containing cell bodies by endogenous adrenergic systems, probably via medullary-pontine alpha-2 adrenergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1983

Strain differences in rat brain epinephrine synthesis: regulation of alpha-adrenergic receptor number by epinephrine.

Inbred tht strains Fischer 344 (F344) and Buffalo (BUF) differ in serveral physiological and behavioral measures. It was found that the activity of adrenomedullary and regional brain phenylethanolamine N-methyltransferase is at least four times higher in F344 rats than in BUF rats; these strain-dependent differences corresponded directly with the epinephrine content of the medulla-pons and hypothalamus. Conversely, alpha-adrenergic receptor density in brain regions containing phenylethanolamine N-methyltransferase is two to three times lower in F344 rats than in BUF rats; alpha-receptors in frontal cortex (a brain region lacking phenylethanolamine N-methyltransferase activity and epinephrine) are similar in both strains. These findings suggest that strain-dependent differences in alpha-receptors are regulated by inherited differences in presynaptic adrenergic neuronal function in different brain regions.

Adrenal Medulla↗