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Biomedical subjects

G Bernardi

Publications and source records attributed to G Bernardi.

At least 91 records · Page 5Linked to original sources
PubMed2003

Migraine-like disorder segregating with mtDNA 14484 Leber hereditary optic neuropathy mutation.

The authors report neurologic features in a large family harboring the mitochondrial DNA (mtDNA) mutation T14484C associated with Leber hereditary optic neuropathy (LHON). In the maternal line the mtDNA mutation was associated with optic neuropathy or migraine with aura or without aura and transient neurologic/visual disturbances. The segregation of familiar cases of migraine and LHON mutation broadens the clinical phenotype associated with a primary LHON mutation.

Adolescent↗
PubMed2003

Preliminary reference levels in interventional cardiology.

This article describes the European DIMOND approach to defining reference levels (RLs) for radiation doses delivered to patients during two types of invasive cardiology procedures, namely coronary angiography (CA) and percutaneous transluminal coronary angioplasty (PTCA). Representative centres of six European countries recorded patients' doses in terms of dose-area product (DAP), fluoroscopy time and number of radiographic exposures, using X-ray equipment that has been subject to constancy testing. In addition, a DAP trigger level for cardiac procedures which should alert the operator to possible skin injury, was set to 300 Gyxcm2. The estimation of maximum skin dose was recommended in the event that a DAP trigger level was likely to be exceeded. The proposed RLs for CA and PTCA were for DAP 45 Gyxcm2 and 75 Gyxcm2, for fluoroscopy time 7.5 min and 17 min and for number of frames 1250 and 1300, respectively. The proposed RLs should be considered as a first approach to help in the optimisation of these procedures. More studies are required to establish certain "tolerances" from the proposed levels taking into account the complexity of the procedure and the patient's size.

Angioplasty, Balloon, Coronary↗
PubMed2003

Decreased plasma and cerebrospinal fluid content of neuroactive steroids in Parkinson's disease.

The levels of the neuroactive steroids allopregnanolone (THP) and 5alpha-dihydroprogesterone (DHP) were quantified in the plasma of 11 (group 1) and in the liquor of 12 (group 2) Parkinson's disease (PD) patients using a gas-chromatographic/mass-spectrometric method. When compared with controls, both groups showed a significant decrease in DHP and THP concentrations. These decreases could be a useful marker of PD. Moreover, in view of the importance of GABA-ergic transmission to substantia nigra (SN) neurons and GABA-ergic modulation exerted by the two neuroactive steroids, our data indicate a global dysregulation of the SN GABA-ergic system in PD patients. Moreover, a lack of neuroprotective factors (i. e., GDNF, BDNF), promoted by DHP, may contribute to dopaminergic cell death.

Aged↗
PubMed2003

alpha-Amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors in spinal cord motor neurons are altered in transgenic mice overexpressing human Cu,Zn superoxide dismutase (Gly93-->Ala) mutation.

There are many evidences implicating glutamatergic toxicity as a contributory factor in the selective neuronal injury occurring in amyotrophic lateral sclerosis (ALS). This neurodegenerative disorder is characterized by the progressive loss of motor neurons, whose pathogenesis is thought to involve Ca(2+) influx mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors (AMPARs). In the present study we report alterations in the AMPARs function in a transgenic mouse-model of the human SOD1(G93A) familial ALS. Compared with those expressed in motor neurons carrying the human wild type gene, AMPAR-gated channels expressed in motor neurons carrying the human mutant gene exhibited modified permeability, altered agonist cooperativity between the sites involved in the process of channel opening and were responsible for slower spontaneous synaptic events. These observations demonstrate that the SOD1(G93A) mutation induces changes in AMPAR functions which may underlie the increased vulnerability of motor neurons to glutamatergic excitotoxicity in ALS.

Alanine↗
PubMed2003

Enkephalin, neurotensin, and substance P immunoreactivite neurones of the rat GP following 6-hydroxydopamine lesion of the substantia nigra.

The ascending dopaminergic tract influences the activity of GP neurones in normal conditions. Its lesion may lead to an up-regulation of activity in this nucleus that is contrary to what would be expected based on the current model of the basal ganglia function. In this study we investigated the occurrence of enkephalin, neurotensin, and substance P immunoreactivity of the rat globus pallidus (GP) following lesion of the nigrostriatal pathway induced by the injection of the toxin 6-hydroxydopamine into the substantia nigra. Since 60-65% of GP neurones are immunopositive for parvalbumin, the immunoreactivity for peptides was evaluated, considering the different content in parvalbumin of pallidal neurones types, at early and chronic phases of denervation. Our results showed that a lesion of the nigrostriatal pathway induced the expression of enkephalin, neurotensin, and substance P immunoreactivity in numerous pallidal cell bodies. Each subgroup of neurones showed a different pattern of distribution. These modifications equally involved the two main subclasses of neurones. However parvalbumin-negative neurones were modified to a larger extent than the parvalbumin-positive ones. These data indicate that nigrostriatal lesion induces in a wide and unexpected peptide synthesis at least in three different subgroups of GP neurones. These modifications might be useful to further histochemically characterise neurones of the GP.

Animals↗
PubMed2003

Lamotrigine and remacemide protect striatal neurons against in vitro ischemia: an electrophysiological study.

In the present study, we investigated the cellular and synaptic mechanisms underlying the neuroprotective action of lamotrigine and remacemide. Both drugs, in fact, have been reported to exert a neuroprotective action in in vivo animal models of ischemia. To address this issue, electrophysiological recordings and cell swelling measurements were performed from striatal neurons in control condition and during combined oxygen and glucose deprivation (in vitro ischemia) in a brain slice preparation. Lamotrigine, remacemide, and the active desglycinyl metabolite of remacemide, D-REMA, induced a concentration-dependent reduction of both repetitive firing discharge and excitatory postsynaptic potentials. However, while remacemide and D-REMA exerted their inhibitory action on glutamatergic transmission by blocking NMDA receptors, lamotrigine exerted a preferential presynaptic action, as indicated by its ability to increase paired-pulse facilitation. Both remacemide and lamotrigine were found to be neuroprotective against the irreversible field potential loss and cell swelling induced by in vitro ischemia, and coadministration of low concentrations of these drugs exerted an additive neuroprotective action. A combined use of lamotrigine and remacemide could be employed in clinical trials to enhance neuroprotection in neurological disorders involving an abnormal striatal glutamatergic transmission.

Acetamides↗
PubMed2003

Corticostriatal LTP requires combined mGluR1 and mGluR5 activation.

Metabotropic glutamate receptors (mGluRs) have been demonstrated to play a role in synaptic plasticity. It has been recently shown that mGluR1 is involved in corticostriatal long-term depression, by means of pharmacological approach and by using mGluR1-knockout mice. Here, we report that both mGluR1 and mGluR5 are involved in corticostriatal long-term potentiation (LTP). In particular, the mGluR1 antagonist LY 367385, as well as the mGluR5 antagonist MPEP, reduce LTP amplitude. Moreover, blockade of both mGluR1 and mGluR5 by LY 367385 and MPEP co-administration fully suppresses LTP. Accordingly, group II and group III mGluRs antagonists fail to affect LTP induction. Interestingly, LTP amplitude is also significantly reduced in both mGluR1- and mGluR5-knockout mice. The differential function of mGluR1 and mGluR5 in corticostriatal synaptic plasticity may play a role in the modulation of the motor activity mediated by the basal ganglia, thus providing a substrate for the pharmacological treatment of motor disorders involving the striatum.

Animals↗
PubMed2003

Targeting striatal cholinergic interneurons in Parkinson's disease: focus on metabotropic glutamate receptors.

In the early sixties, anticholinergic drugs were introduced in the pharmacological treatment of Parkinson's disease (PD). The rationale behind their utilisation in the treatment of the disease was based on the evidence of an imbalance between the dopaminergic inputs and the intrinsic cholinergic innervation within the striatum. Metabotropic glutamate (mGlu) receptors have been shown to play a key role in striatal function both in physiological conditions and in experimental models of diseases affecting this brain area. Indeed, compelling electrophysiological and morphological evidence shows that mGlu receptors are highly expressed at cellular level and exert a profound modulatory role on cholinergic interneurons excitability. This review will provide a brief survey of studies on the localization and function of mGlu receptors in cholinergic interneurons. The potential relevance of these findings in the control of motor function and in the treatment of PD will be discussed.

Acetylcholine↗
PubMed2003

Altered long-term corticostriatal synaptic plasticity in transgenic mice overexpressing human CU/ZN superoxide dismutase (GLY(93)-->ALA) mutation.

Apart from the extensive loss of motor neurons, degeneration of midbrain dopaminergic cells has been described in both familial and sporadic forms of amyotrophic lateral sclerosis (ALS). Mice overexpressing the mutant human Cu/Zn superoxide dismutase (SOD1) show an ALS-like phenotype in that they show a progressive death of motor neurons accompanied by degeneration of dopaminergic cells. To describe the functional alterations specifically associated with this dopaminergic dysfunction, we have investigated the corticostriatal synaptic plasticity in mice overexpressing the human SOD1 (SOD1+) and the mutated (Gly(93)-->Ala) form (G93A+) of the same enzyme. We show that repetitive stimulation of the corticostriatal pathway generates long-term depression (LTD) in SOD1+ mice and in control (G93A-/SOD1-) animals, whereas in G93A+ mice the same stimulation generates an N-methyl-D-aspartic acid receptor-dependent long-term potentiation. No significant alterations were found in the intrinsic membrane properties of striatal medium spiny neurons and basal corticostriatal synaptic transmission of G93A+ mice. Bath perfusion of dopamine or the D(2) dopamine receptor agonist quinpirole restored LTD in G93A+ mice. Consistent with these in vitro results, habituation of locomotor activity and striatal-dependent active avoidance learning were impaired in G93A+ mice. Thus, degeneration of dopaminergic neurons in the substantia nigra of G93A+ mice causes substantial modifications in striatal synaptic plasticity and related behaviors, and may be a cellular substrate of the extrapyramidal motor and cognitive disorders observed in familial and sporadic ALS.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2003

Up-regulation of P2X2, P2X4 receptor and ischemic cell death: prevention by P2 antagonists.

In the present work we examined the involvement of selected P2X receptors for extracellular ATP in the onset of neuronal cell death caused by glucose/oxygen deprivation. The in vitro studies of organotypic cultures from hippocampus evidenced that P2X2 and P2X4 were up-regulated by glucose/oxygen deprivation. Moreover, we showed that ischemic conditions induced specific neuronal loss not only in hippocampal, but also in cortical and striatal organotypic cultures and the P2 receptor antagonists basilen blue and suramin prevented these detrimental effects. In the in vivo experiments we confirmed the induction of P2X receptors in the hippocampus of gerbils subjected to bilateral common carotid occlusion. In particular, P2X2 and P2X4 proteins became significantly up-regulated, although to different extent and in different cellular phenotypes. The induction was confined to the pyramidal cell layer of the CA1 subfield and to the transition zone of the CA2 subfield and it was coincident with the area of neuronal damage. P2X2 was expressed in neuronal cell bodies and fibers in the CA1 pyramidal cell layer and in the strata oriens and radiatum. Intense P2X4 immunofluorescence was localized to microglia cells. Our results indicate a direct involvement of P2X receptors in the mechanisms sustaining cell death evoked by metabolism impairment and suggest the use of selected P2 antagonists as effective neuroprotecting agents.

Animals↗
PubMed2003

Reductions in the mitochondrial DNA diversity of coral reef fish provide evidence of population bottlenecks resulting from Holocene sea-level change.

This study investigated the influence of reproductive strategy (benthic or pelagic eggs) and habitat preferences (lagoon or outer slope) on both diversity and genetic differentiation using a set of populations of seven coral reef fish species over different geographic scales within French Polynesia. We hypothesized that a Holocene sea-level decrease contributed to severe reduction of population size for species inhabiting lagoons and a subsequent decrease of genetic diversity. Conversely, we proposed that species inhabiting stable environments, such as the outer slope, should demonstrate higher genetic diversity but also more structured populations because they have potentially reached a migration-genetic drift equilibrium. Sequences of the 5' end of the mitochondrial DNA (mtDNA) control region were compared among populations sampled in five isolated islands within two archipelagos of French Polynesia. For all the species, no significant divergences among populations were found. Significant differences in mtDNA diversity between lagoonal and outer-slope species were demonstrated both for haplotype diversity and sequence divergence but none were found between species with different egg types. Pairwise mismatch distributions suggested rapid population growth for all the seven species involved in this study, but they revealed different distributions, depending on the habitat preference of the species. Although several scenarios can explain the observed patterns, the hypothesis of population size reduction events relative to Holocene sea-level regression and its consequence on French Polynesia coral reefs is the most parsimonious. Outer-slope species have undergone a probable weak and/or old bottleneck (outer reefs persisted during low sea level, leading to reef area reductions), whereas lagoonal species suffered a strong and/or recent bottleneck since Holocene sea-level regression resulted in the drying out of all the atolls that are maximum 70 meters deep. Since present sea level was reached between 5000 and 6000 years ago, different demographic events (bottlenecks or founder events) have lead to the actual populations of lagoons in French Polynesia.

Animals↗
PubMed2003

Depression of mGluR-mediated IPSCs by 5-HT in dopamine neurons of the rat substantia nigra pars compacta.

Dopamine neurons of the substantia nigra pars compacta receive a prominent serotonin (5-HT) projection from the dorsal raphe nucleus and important functional interactions between the serotonergic and the dopaminergic system have been postulated. In the present report we examined the role of 5-HT in the modulation of the metabotropic glutamate receptor-mediated inhibitory postsynaptic current (mGluR-IPSC) in midbrain dopamine neurons, and we found a reversible depression of this synaptic response at concentrations of 5-HT ranging from 100 nm to 30 microm (EC50 1.06 microm). This resulted in a shift towards excitation of the overall dopamine neuron response to glutamatergic synaptic input. This effect was not because of a direct modulation of the Ca2+-sensitive K+ conductances underlying the mGluR-IPSC, but was associated with a decrease in the intracellular calcium signal triggered by mGluR stimulation. Similar results were obtained with alpha-methyl-5-hydroxytryptamine and 5-methoxytryptamine, but not with 5-carboxamidotryptamine or 1-(3-chlorophenyl) piperazine. No significant depression of the mGluR-IPSC by 5-HT was observed in the presence of the 5-HT2 antagonist cinanserin or the 5-HT4 receptor antagonist RS 23597-190, whereas the 5-HT2C antagonist RS 102221 was ineffective. Our results demonstrate a powerful inhibition of the mGluR-IPSC by 5-HT in midbrain dopamine neurons, most probably through stimulation of 5-HT2A and 5-HT4 receptors.

Animals↗
PubMed2003

GABA(A) receptor active steroids are altered in epilepsy patients with tuberous sclerosis.

BACKGROUND: The neuroactive steroid 3alpha, 5alpha-tetrahydroprogesterone is the most potent endogenous positive modulator of gamma-amino-butyric acid (GABA)(A) receptors. There is evidence for a relation between neuroactive steroids and seizure susceptibility. OBJECTIVE: To evaluate the putative role of counteregulator neuroactive steroids in the occurrence of seizures in patients with tuberous sclerosis. METHODS: Plasma concentrations of the enantiomers 3alpha, 5alpha- and 3alpha, 5beta-tetrahydroprogesterone (3alpha(s)-THP), which are positive modulators of GABA(A) receptors, were measured in 18 patients, along with their endogenous functional antagonists 3beta, 5alpha- and 3beta, 5beta-THP (3beta(s)-THP), to assess their possible modification compared with control subjects. Neuroactive steroids were assayed using a highly sensitive and specific gas chromatographic/mass spectrometric method. RESULTS: In the tuberous sclerosis patients with poorly controlled seizures, there was a significantly lower 3alpha(s)/3beta(s)-THP ratio than in seizure-free patients or control subjects. CONCLUSIONS: The reduced 3alpha(s)/3beta(s)-THP ratio may decrease GABAergic tone, contributing to the appearance of seizures in tuberous sclerosis patients with epilepsy.

Adolescent↗
PubMed2003

[Comparative compositional mapping of chicken and quail chromosomes].

The distribution of various isochore families on mitotic chromosomes of domestic chicken and Japanese quail was studied by the method of fluorescence in situ DNA--DNA hybridization (FISH). DNA of various isochore families was shown to be distributed irregularly and similarly on chromosomes of domestic chicken and Japanese quail. The GC-rich isochore families (H2, H3, and H4) hybridized mainly to microchromosomes and a majority of macrochromosome telomeric regions. In chicken, an intense fluorescence was also in a structural heterochromatin region of the Z chromosome long arm. In some regions of the quail macrochromosome arms, hybridization was also with isochore families H3 and H4. On macrochromosomes of both species, the pattern of hybridization with isochores of the H2 and H3 families resembled R-banding. The light isochores (L1 and L2 families) are mostly detected within macrochromosome internal regions corresponding to G bands, whereas microchromosomes lack light isochores. Although mammalian and avian karyotypes differ significantly in organization, the isochore distribution in genomes of these two lineages of the warm-blooded animals is similar in principle. On macrochromosomes of the two avian species studied, a pattern of isochore distribution resembled that of mammalian chromosomes. The main specific feature of the avian genome, a great number of microchromosomes (about 30% of the genome), determines a compositional specialization of the latter. This suggests the existence of not only structural but also functional compartmentalization of the avian genome.

Animals↗
PubMed2002

Search for the production of single sleptons through R-parity violation in pp; collisions at square root (s) =1.8 TeV.

We report the first search for supersymmetric particles via s-channel production and decay of smuons or muon sneutrinos at hadronic colliders. The data for the two-muon and two-jets final states were collected by the D0 experiment and correspond to an integrated luminosity of 94+/-5 pb(-1). Assuming that R parity is violated via the single coupling lambda'211, the number of candidate events is in agreement with expectation from the standard model. Exclusion contours are given in the (m(0),m(1/2)) and (m(x),m(v)) planes for lambda(')(211)=0.09, 0.08, and 0.07.

Journal Article↗
PubMed2002

Clinical and genetic study of a large Italian family linked to SPG12 locus.

BACKGROUND: Seven loci for autosomal dominant hereditary spastic paraplegia (ADHSP) have been mapped. To date, two families of SPG12 (chromosome 19q13) have been analyzed; however, there is not enough clinical information on SPG12 to establish locus-phenotype correlations. METHODS: The authors studied 60 individuals from a large Italian family with ADHSP, in which 16 members in four generations were affected. They performed genetic linkage analysis with DNA markers from currently known ADHSP loci. After database searching, one candidate gene for SPG12 was analyzed by sequencing. RESULTS: The patients in this family showed an early onset and rapid progression of symptoms, resulting in severe disability, with a large proportion of affected members requiring use of a wheelchair. By age 16, most patients had sensory disturbance. Evidence for linkage to the SPG12 locus was obtained. Obligate recombination events observed in this family have narrowed the SPG12 locus from the 16.1 cM to 11.3 cM region between markers D19S416 and D19S412. In combination with previous genetic studies, the SPG12 locus was further narrowed to the 3.3 cM region between D19S416 and D19S220. A homologue of the AAA (ATPases associated with a variety of cellular activities) protein family, proteasome 26S subunit ATPase mapped near D19S220, was excluded by sequencing. CONCLUSIONS: This study refined the SPG12 region between D19S416 and D19S220 and revealed several clinical characteristics-early onset, rapid progression, and involvement of sensory disturbance-that may be unique to SPG12. Suggestive evidence of genetic anticipation was obtained, but should be confirmed in other SPG12 families.

Adenosine Triphosphatases↗
PubMed2002

Search for R-parity violating supersymmetry in two-muon and four-jet topologies.

We present results of a search for R-parity-violating decay of the neutralino chi;01, taken as the lightest supersymmetric particle, to a muon and two jets. The decay proceeds through a lepton-number violating coupling lambda(')(2jk) (j=1,2; k=1,2,3), with R-parity conservation in all other production and decay processes. In the absence of candidate events from 77.5+/-3.9 pb(-1) of data collected by the D0 experiment at the Fermilab Tevatron in pp collisions at sqrt[s]=1.8 TeV, and with an expected background of 0.18+/-0.03+/-0.02 events, we set limits on squark and gluino masses within the framework of the minimal low-energy supergravity-supersymmetry model.

Journal Article↗