Search PubMed⌕ Search

Biomedical subjects

A Pisani

Publications and source records attributed to A Pisani.

At least 109 records · Page 6Linked to original sources
PubMed1995

Transmitter release associated with long-term synaptic depression in rat corticostriatal slices.

Using a corticostriatal slice preparation, we have recently shown that tetanic stimulation of the corticostriatal pathway produces long-term depression (LTD) of striatal excitatory synaptic transmission. In the present study we have analysed the relationship between LTD and the striatal release of different endogenous transmitters. Samples of perfusate were collected via a small cannula placed just above the surface of the striatal slice close to the recording electrode, and were analysed by HPLC. The high-frequency stimulation (100 Hz, three trains, 3 s duration, 20 s interval) used to induce LTd caused a significant but transient increase in the release of both excitatory (aspartate and glutamate) and inhibitory (glycine and GABA) amino acid transmitters. Tetanic stimulation also produced a significant, but transient increase in the release of endogenous dopamine. We conclude that the tetanic stimulation of the corticostriatal pathway is able to induce a large but transient release of excitatory amino acids and of dopamine, whose participation in the induction of striatal LTD has been demonstrated previously. Moreover, the maintenance of this form of synaptic plasticity does not seem to require a sustained change in transmitter release.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Vulnerability of medium spiny striatal neurons to glutamate: role of Na+/K+ ATPase.

In Huntington's disease neuronal degeneration mainly involves medium-sized spiny neurons. It has been postulated that both excitotoxic mechanisms and energy metabolism failure are implicated in the neuronal degeneration observed in Huntington's disease. In central neurons, > 40% of the energy released by respiration is used by Na+/K+ ATPase to maintain ionic gradients. Considering that impairment of Na+/K+ ATPase activity might alter postsynaptic responsivity to excitatory amino acids (EAAs), we investigated the effects of the Na+/K+ ATPase inhibitors, ouabain and strophanthidin, on the responses to different agonists of EAA receptors in identified medium-sized spiny neurons electrophysiologically recorded in the current- and voltage-clamp modes. In most of the cells both ouabain and strophanthidin (1-3 microM) did not cause significant change in the membrane properties of the recorded neurons. Higher doses of either ouabain (30 microM) or strophanthidin (30 microM) induced, per se, an irreversible inward current coupled to an increase in conductance, leading to cell deterioration. Moreover, both ouabain (1-10 microM) and strophanthidin (1-10 microM) dramatically increased the membrane depolarization and the inward current produced by subcritical concentrations of glutamate, AMPA and NMDA. These concentrations of Na+/K+ ATPase inhibitors also increased the membrane responses induced by repetitive cortical activation. In addition, since it had previously been proposed that dopamine mimics the effects of Na+/K+ ATPase inhibitors and that dopamine agonists differentially regulate the postsynaptic responses to EAAs, we tested the possible modulation of EAA-induced membrane depolarization and inward current by dopamine agonists. Neither dopamine nor selective dopamine agonists or antagonists affected the postsynaptic responses to EAAs. Our experiments show that impairment of the activity of Na+/K+ ATPase may render striatal neurons more sensitive to the action of glutamate, lowering the threshold for the excitotoxic events. Our data support neither the role of dopamine as an ouabain-like agent nor the differential modulatory action of dopamine receptors on the EAA-induced responses in the striatum.

Animals↗
PubMed1995

Outward potassium currents activated by depolarization in rat globus pallidus.

Voltage-dependent potassium currents play a key role in shaping the firing pattern of central neurons. Their pharmacological and physiological identification is rather important in the structures which are involved in the filtering of input/output messages. In this regard, globus pallidus external segment (GPe) is indicated as a crucial station in the well-known indirect pathway of the basal ganglia. Among the potassium conductances which have been indicated to condition the firing behavior and the neuronal integrative properties in many central neurons, we analysed the depolarization-activated ones by means of patch-clamp recordings in the whole-cell configuration. Two main families of calcium-independent outward potassium currents are activated by depolarization in GPe neurons acutely isolated from the adult rat. From depolarized holding potentials (-50/-45 mV), a slowly-activating, sustained current is evoked; it manifests very little inactivation and it is available at rather depolarized potentials (-30 mV/-20 mV). This current is relatively resistant to 4-aminopyridine (4-AP) but it is blocked by tetraethilammonium ions (TEA) and consequently it resembles delayed rectifier current (Ik). From negative holding potentials (-80/-100 mV), on the other hand, A-like conductances are activated. Together with a fast-inactivating transient current, another component is observed in a significant proportion of recordings (45%). This current shows half-inactivation voltage around -90 mV, peculiar sensitivity to micromolar doses of 4-AP and a slow rate of recovery from inactivation. The presence and the modulation of these A-like currents may be a very critical aspect in the membrane physiology of pallidal neurons.

4-Aminopyridine↗
PubMed1995

Clinical and MRI assessment of disease activity in patients with multiple sclerosis after influenza vaccination.

We investigated the possible effects of influenza vaccination on disease activity in multiple sclerosis (MS). Six patients were evaluated clinically during the year preceding and the year following influenza vaccination. Gadolinium-enhanced magnetic resonance imaging (Gd-MRI) was performed one day before and at days 15 and 45 after vaccination. Cumulatively, we did not observe increases in clinical or MRI disease activity following vaccination, with the exception of one case. This was the patient with the highest clinical disease activity during the year preceding vaccination. These results support and supplement previous observations, indicating that influenza vaccination is a safe procedure in multiple sclerosis. Nevertheless, it should be used with caution in patients with active/progressing disease.

Adult↗
PubMed1995

Electrophysiology of dopamine D-1 receptors in the basal ganglia: old facts and new perspectives.

1. The dopamine (DA) D1-receptor family is highly represented in the mammalian brain and particularly in the nigrostriatal system, whose integrity is crucial for the execution of motor performances. 2. In the last decade, our understanding of the electrophysiology of D1 receptors on caudate-putamen neurons has greatly improved. The effects of the activation of striatal D1 receptors were studied by extracellular single unit recordings in the intact animal as well as by intracellular recordings in rat brain slice preparation. More recently, whole-cell recordings on isolated striatal neurons have further addressed this issue and confirmed the inhibitory modulatory role of D1 receptor on the electrical activity of striatal neurons. 3. Several important questions, however, concerning the functional effects of D1 receptor activation in the basal ganglia are still debated: the cellular segregation of the distribution of D1-D2-like receptors, their synergistic or opposite functional roles at the second messenger level, the effects of D1 receptor activation on the transmitter release and the modifications of D1 receptor pharmacology in dopamine-denervated striata. 4. A different perspective will also be discussed: the involvement of D1 receptors in long-term changes of synaptic efficacy in the striatum as a possible correlate of motor learning.

Animals↗
PubMed1995

Transition from asymptomatic left ventricular dysfunction to congestive heart failure.

One of the main goals of modern management and care of heart failure is to prevent the disease to progress toward congestion and death. The achievement of such an objective may, in fact, guarantee a sufficient quality of life and reduce the exposure of patients to the most common life-threatening complications associated with the congestive stage of the disease. Early identification of left ventricular dysfunction as well as a better knowledge of the mechanisms that favor the progression to more advanced stages of heart failure are fundamental requirements for the proper treatment of asymptomatic heart failure and for preventing the transition to symptomatic and more severe heart failure. The authors reviewed the literature on this topic, with emphasis on a series of studies they performed, to characterize the pathophysiologic profile of mild heart failure and the mechanisms that are possibly involved in the progression to congestive heart failure.

Adaptation, Physiological↗
PubMed1995

Hypoxia-induced electrical changes in striatal neurons.

We have studied the effects of hypoxia on the membrane properties of striatal neurons intracellularly recorded from a corticostriatal slice preparation. Brief (2-10 min) periods of hypoxia produced reversible membrane depolarizations. Longer periods of hypoxia (12-20 min) produced irreversible membrane depolarizations. In voltage-clamp experiments, hypoxia caused an inward current coupled with an increased membrane conductance. Tetrodotoxin or low calcium (Ca2+)-high magnesium-containing solutions blocked synaptic transmission, but they did not reduce the hypoxia-induced electrical changes. Antagonists of excitatory amino acid (EAA) receptors failed to affect the electrical effects caused by oxygen (O2) deprivation. In low sodium (Na+)-containing solutions the hypoxia-induced inward current was largely reduced. Blockade of ATP-dependent Na(+)-potassium (K+) pump by ouabain enhanced hypoxia-induced membrane depolarizations and/or inward currents. Our findings indicate that, at least for in vitro experiments, the release of EAAs is not required for the acute hypoxia-induced electrical changes in striatal neurons.

Animals↗
PubMed1995

On the mechanisms underlying hypoxia-induced membrane depolarization in striatal neurons.

Clinical and experimental evidence has shown that the striatal neurons are particularly vulnerable to hypoxia and ischaemia. An excessive excitatory action of glutamate, released by the corticostriatal terminals, has been implicated in this peculiar vulnerability of striatal neurons. We have studied the effects of hypoxia on the membrane properties of striatal neurons intracellularly recorded from a corticostriatal slice preparation. Brief (2-10 min) periods of hypoxia produced reversible membrane depolarizations. During the initial phase of the hypoxia-induced depolarization the frequency of action potential discharge was transiently increased; 2-3 min after the onset of hypoxia the firing activity was fully abolished. Brief periods of hypoxia also caused a reversible reduction of the amplitude of the excitatory postsynaptic potentials (EPSPs) evoked by cortical stimulation. Longer period of hypoxia (12-20 min) produced irreversible membrane depolarizations. In voltage-clamp experiments hypoxia caused an inward current coupled with an increased membrane conductance. Tetrodotoxin (TTX) or low calcium (Ca2+)-high magnesium containing solutions blocked synaptic transmission, but they did not reduce the hypoxia-induced electrical changes. Antagonists of excitatory amino acid receptors failed to affect the electrical effects caused by oxygen deprivation. Hypoxia-induced inward currents were reduced either by the potassium (K+) channel blockers, barium and tetraethyl ammonium (TEA) cations, or by lowering external sodium (Na+) concentration. Blockade of ATP-dependent Na(+)-K+ pump by both ouabain and strophanthidin enhanced hypoxia-induced membrane depolarization/inward current. Our findings indicate that the release of excitatory amino acids does not seem to be required for the acute hypoxia-induced electrical changes in striatal neurons. Moreover, TTX-resistant Na+ influx and K+ currents seem to play an important role in the generation of hypoxia-induced electrical changes. These data also suggest that the selective vulnerability of striatal neurons to oxygen deprivation may be caused by their peculiar sensitivity to energy metabolism failure.

Animals↗
PubMed1995

Electrophysiological actions of felbamate on rat striatal neurones.

1. We have investigated the effects of the anticonvulsant drug, felbamate (FBM), on striatal neurones, recorded in vitro by using both intracellular and extracellular conventional recordings in slices and whole-cell recordings in acutely isolated neurones. 2. FBM, at therapeutically relevant concentrations (30-300 microM) showed multiple mechanisms of action. Like other antiepileptic drugs, FBM (30-300 microM) showed a direct inhibitory action on current-evoked firing discharge of striatal neurones. A patch-clamp analysis of this effect revealed a dose-related reduction of voltage-dependent sodium (Na+) currents (10-100 microM), with a half inhibiton dose (IC50) value of 28 microM. 3. We also tested whether FBM affected corticostriatal glutamate transmission. In control medium (1.2 mM external magnesium), both extracellularly recorded field potentials and intracellularly recorded excitatory postsynaptic potentials (e.p.s.ps) evoked by cortical stimulation were no affected by bath application of 30-300 microM FBM. 4. When magnesium was removed from the perfusing solution, a procedure which reveals a N-methyl-D-aspartate (NMDA)-mediated component in the corticostriatal synaptic potential, FBM (30-300 microM) produced a dose-dependent reduction of the amplitude of both the field potential and the e.p.s.p. 5. FBM reduced the inward currents produced either by bath or by focal applications of 30 microM NMDA, finding consistent with the hypothesis that the observed reduction of the NMDA-mediated component of the synaptic potentials may be caused at postsynaptic level. 6. The reduction of the NMDA-mediated component of the synaptic transmission by FBM and its depressant effect on the voltage-dependent Na+ channels, may account for the antiepileptic action of this drug. Moreover, the pharmacological properties of FBM might render this drug interesting as a neuroprotectant agent.

Action Potentials↗
PubMed1995

Childhood acquired epidermolysis bullosa.

We present the ninth case of epidermolysis bullosa acquisita (EBA) reported in children. As in most of the other childhood cases, the 7-year-old boy described herein had an acute, widespread, inflammatory vesiculobullous eruption with oral involvement. Indirect immunofluorescence on salt-split skin as well as Western immunoblot confirmed the diagnosis of EBA. The patient responded to combined prednisone and dapsone, and was maintained with dapsone alone.

Administration, Oral↗
PubMed1995

Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. I. Modulation of corticostriatal synaptic transmission.

Oxcarbazepine (OCBZ) is the keto-analogue of carbamazepine (CBZ). In humans, OCBZ is rapidly and almost completely metabolized to 10, 11-dihydro-10-hydroxy-CBZ (GP 47779), the main metabolite responsible for the drug's antiepileptic activity. The corticostriatal pathway is involved in the propagation of epileptic discharges. We characterized the electrophysiological effects of GP 47779 on striatal neurons by making intracellular recordings from corticostriatal slices. GP 47779 (3-100 microM) produced a dose-dependent inhibition of glutamatergic excitatory postsynaptic potentials (EPSPs). This effect was not coupled either with changes of the membrane potential of these cells or with alterations of their postsynaptic sensitivity to excitatory amino acids (EAA) suggesting a presynaptic site of action. GP 47779 reduced the current-evoked firing discharge only at concentrations > 100 microM. GP 47779 did not affect the presynaptic inhibitory action of adenosine, showing that presynaptic adenosine receptors were not implicated in the GP 47779-mediated reduction of corticostriatal EPSPs. Our data indicate that GP 47779 apparently acts directly on corticostriatal terminals to reduce the release of EAA, probably by inhibiting high-voltage-activated (HVA) calcium (Ca2+) currents (described in the accompanying article). The inhibitory action of GP 47779 on corticostriatal transmission may contribute to the antiepileptic effects of this drug.

Adenosine↗
PubMed1995

Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. II. Modulation of high-voltage-activated calcium currents.

GP 47779, the active metabolite of oxcarbazepine (OCBZ) inhibits glutamatergic excitatory postsynaptic potentials (EPSPs) in rat striatum (described in the accompanying article). This effect was presumed to involve the modulation of the calcium (Ca2+) signals at either pre- or postsynaptic level. Therefore, we directly tested whether GP 47779 could modulate Ca2+ conductances in cortical as well as in striatal neurons. GP 47779 produced a reversible dose-dependent decrease in high-voltage-activated (HVA) Ca2+ currents evoked by membrane depolarization in isolated cortical pyramidal cells. GP 47779-mediated reduction in HVA Ca2+ currents, if occurring also at corticostriatal axon terminals, might explain the reduction of glutamate release in the striatum. An inhibitory action of GP 47779 on HVA Ca2+ currents was also observed in isolated striatal neurons. The effect of HVA Ca2+ currents in cortical and striatal neurons persisted in the presence of nifedipine, suggesting that dihydropyridine-sensitive channels were not involved in the GP 47779-mediated responses. We propose that the modulation of HVA Ca2+ channels by this carbamazepine (CBZ) analogue may account for its inhibitory action on transmitter release.

Animals↗
PubMed1995

[Synergism between cyclosporin and gangliosides in anti-rejection therapy. Experimental in vivo model].

In vivo gangliosides (GS) bring about inhibitory effects on the immune response which is attributable to a weakening of the interaction between interleukin-2 (IL-2) and its receptor. In a previous paper we showed that the GS are capable of bringing about in vitro the immunosuppressive power of cyclosporin A CyA2 in this paper we have tried to associate gangliosides (GS) and low dose of CyA in the grafting of rat allogen cutis in order to have in this way in vivo a confirmation of the results previously obtained in vitro. Cutaneous strips taken from Lewis rats were grafted into Sprague Dawley rats and treated for 21 days with intraperitoneal administration of GS, of Cya, and a mixture of the two. The rats were not treated and the rats treated with GS and with CyA separately rejected the graft of the cutis. On the other hand, the use of an association of Gs and CyA brought about a successful graft in 8 rats out of 10. Splenic cells extracted 21 days after the graft from rats treated with GS and with CyA separately were stimulated in vitro with Packweed mitogen (PWM); on the contrary the cells extracted from rats treated with a combination of the two drugs did not react to the stimulation with PWM. Our results show that the GS brings about in vivo the immunosuppressive effects of low doses of CyA.

Animals↗
PubMed1995

The modulation of dopamine receptors in rat striatum.

In the last decades, the contribution given by basic electrophysiology to the understanding of the nigrostriatal pathway in mammals has been rather important. The main results obtained by our group will be revised in this short review. The most common responses produced by dopamine (DA) on the principal striatal cells (the medium spiny neurons) are the modulation of the corticostriatal synaptic transmission and the decrease of voltage-dependent inward conductances. After blockade of DA transmission, both spontaneous and cortically driven glutamatergic postsynaptic potentials were inhibited by the selective activation of DA D2 receptors. In naive animals, the DA-mediated inhibition of postsynaptic firing activity was mediated by D1 receptor activation. Nevertheless, the two main subclasses of DA receptors seemed to cooperate in the formation of the long-term depression (LTD) of excitatory synaptic transmission in the striatum. The excitotoxic hypothesis of neurodegeneration has further stimulated our interest towards the study of the interactions between DA and other neurotransmitters into the basal ganglia.

Animals↗
PubMed1994

Protective effect of glutathione on kainic acid-induced neuropathological changes in the rat brain.

1. Glutathione (GSH), injected by slow intravenous (i.v.) infusion (7.9 microliters/min, for 4 hr; total dose: 1.5 g/kg), starting 10 min after i.v. injection of kainic acid (KA; 12 mg/kg) in the rat reduced the decrease in local cerebral glucose utilization observed 48 hr following the administration of the neurotoxin. 2. Furthermore, it blocked the neuronal loss in hippocampal CA1 and CA3 regions, and prevented, in the hippocampus, the development of edema and the marked depletion in the endogenous brain GSH pool. 3. One can speculate that this protective effect of exogenous GSH is correlated to its capacity to scavenge free radicals, thus preventing the accumulation of oxidant chemical species and the consequent reduction of cellular antioxidant defense.

Animals↗
PubMed1994

Expression of integrins in human nail matrix.

The aim of this study was to characterize cell-cell and cell-matrix interaction by evaluating the expression of different integrins in the nail matrix. Nail biopsies were obtained from two cadaver fingers, and eight patients with ingrowing toenails. Frozen sections were stained by indirect immunofluorescence using anti-alpha 1, anti-alpha 2, anti-alpha 3, anti-alpha 4, anti-alpha 5, anti-alpha 6, anti-alpha v, anti-beta 1, anti-beta 4 and anti-ICAM-1 monoclonal antibodies. Biopsies from normal human foreskin were evaluated as controls. alpha 1, alpha 4 and alpha 5 subunits were absent from both nail matrix and normal human skin. alpha 2, alpha 3 and beta 1 subunits were expressed in the basal and suprabasal layers of nail matrix, but only in the basal layer of skin epidermis. alpha 6 and beta 4 subunits were strongly expressed in the basement membrane zone and in the basal layer of both nail matrix and epidermis. The alpha v subunit was expressed in the basal layer of nail matrix. ICAM-1 was not expressed in nail matrix epidermis. Our findings show that despite the distinctive features of the nail apparatus, compared with the epidermis, the pattern of integrin expression is similar, although some differences in the distribution of alpha 2, alpha 3 and beta 1 subunits are detectable. These are probably related to the peculiar differentiation and keratinization of the nail.

Basement Membrane↗
PubMed1994

Activation of metabotropic glutamate receptors inhibits calcium currents and GABA-mediated synaptic potentials in striatal neurons.

The transmitter release from GABAergic synapses is thought to be calcium (Ca2+) dependent. The pharmacological modulation of Ca2+ currents in central GABAergic neurons may strongly affect GABA release from synaptic sites. The source of striatal GABA-containing synapses is intrinsic to the striatum and mainly originates from axon collaterals of projecting medium-spiny neurons. In order to characterize the role of metabotropic glutamate receptors (mGluRs) in the modulation of central GABA release, we have combined the study of high-voltage-activated (HVA) Ca2+ currents in isolated striatal neurons with the analysis of GABA-mediated synaptic potentials evoked by local stimulation in striatal slices. The mGluR agonists t-ACPD and 1S,3R-ACPD produced a reversible and dose-dependent decrease of both HVA Ca2+ currents and GABA-mediated synaptic potentials. The mGluR-mediated inhibition of GABA-mediated synaptic potentials was not coupled with changes of the membrane responses to exogenously applied GABA, suggesting an effect on the transmitter release rather than on the GABA receptor sensitivity. The reduction of Ca2+ currents persisted in nifedipine, but not in omega-conotoxin, supporting the involvement of an N-type Ca2+ channel in this pharmacological effect. The GABA-mediated synaptic potentials were greatly reduced by omega-conotoxin. The inhibitory action of 1S,3R-ACPD on residual GABA-mediated potentials was fully occluded in the presence of omega-conotoxin. In neurons dialyzed with GTP-gamma-S, the reduction of HVA currents was irreversible, suggesting an involvement of a G-protein-mediated mechanism. Preincubation in staurosporine blocked neither the reduction of Ca2+ currents nor the inhibition of synaptic potentials induced by mGluR activation, suggesting that staurosporine-sensitive kinases are not involved in these actions. L-AP3, a noncompetitive antagonist of mGluR-mediated alteration of phosphoinositide (PI) hydrolysis, failed to block both the mGluR-mediated reduction of Ca2+ current and the inhibition of GABA-mediated synaptic potentials. We conclude that activation of mGluRs depresses intrastriatal GA-BAergic transmission and Ca2+ currents recorded from putative GABAergic striatal cells. We suggest that a reduction of Ca2+ influx in the striatal GABAergic terminal may account for the mGluR-mediated inhibition of synaptic GABA release in this structure. The modulation of GABA release by mGluRs may have a profound implication in the physiopathology of basal ganglia activity.

Alanine↗