Graziella Madeo

Publications (13) View all

• Article: Early abnormalities in 123I-ioflupane (DaTSCAN) imaging in the fragile X-associated tremor ataxia syndrome (FXTAS): a case report.

  G Madeo, F Alemseged, B Di Pietro, O Schillaci, A Pisani
  Neurological Sciences 10/2012; · 1.32 Impact Factor
• Article: Cholinergic dysfunction alters synaptic integration between thalamostriatal and corticostriatal inputs in DYT1 dystonia.

  Giuseppe Sciamanna, Annalisa Tassone, Georgia Mandolesi, Francesca Puglisi, Giulia Ponterio, Giuseppina Martella, Graziella Madeo, Giorgio Bernardi, David G Standaert, Paola Bonsi, Antonio Pisani
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  ABSTRACT: Projections from thalamic intralaminar nuclei convey sensory signals to striatal cholinergic interneurons. These neurons respond with a pause in their pacemaking activity, enabling synaptic integration with cortical inputs to medium spiny neurons (MSNs), thus playing a crucial role in motor function. In mice with the DYT1 dystonia mutation, stimulation of thalamostriatal axons, mimicking a response to salient events, evoked a shortened pause and triggered an abnormal spiking activity in interneurons. This altered pattern caused a significant rearrangement of the temporal sequence of synaptic activity mediated by M(1) and M(2) muscarinic receptors in MSNs, consisting of an increase in postsynaptic currents and a decrease of presynaptic inhibition, respectively. Consistent with a major role of acetylcholine, either lowering cholinergic tone or antagonizing postsynaptic M(1) muscarinic receptors normalized synaptic activity. Our data demonstrate an abnormal time window for synaptic integration between thalamostriatal and corticostriatal inputs, which might alter the action selection process, thereby predisposing DYT1 gene mutation carriers to develop dystonic movements.
  Journal of Neuroscience 08/2012; 32(35):11991-2004. · 7.11 Impact Factor
• Article: Aberrant striatal synaptic plasticity in monogenic parkinsonisms.

  G Madeo, G Martella, T Schirinzi, G Ponterio, J Shen, P Bonsi, A Pisani
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  ABSTRACT: In the recent past, the pathogenesis of Parkinson's disease (PD) has evolved from a neurodegenerative disorder considered entirely sporadic to a disease with an unequivocal genetic component. Indeed, different inherited forms of PD have been discovered and characterized, although the functional roles of the gene products identified are still under intense investigation. To gain a better understanding of the cellular and molecular pathogenic mechanisms of hereditary forms of PD, different animal models have been generated. Although most of the rodent models display neither obvious behavioral impairment nor evidence for neurodegeneration, remarkable abnormalities of dopamine-mediated neurotransmission and corticostriatal synaptic plasticity have been described, indicative of a fundamental distortion of network function within the basal ganglia. The picture emerging from a critical review of recent data on monogenic parkinsonisms suggests that mutations in PD genes might cause developmental rearrangements in the corticobasal ganglia circuitry, compensating the dopaminergic dysfunction observed both in mice and humans, in order to maintain proper motor function.
  Neuroscience 08/2011; 211:126-35. · 3.38 Impact Factor
• Article: Altered profile and D2-dopamine receptor modulation of high voltage-activated calcium current in striatal medium spiny neurons from animal models of Parkinson's disease.

  G Martella, G Madeo, T Schirinzi, A Tassone, G Sciamanna, F Spadoni, A Stefani, J Shen, A Pisani, P Bonsi
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  ABSTRACT: In the present work we analyzed the profile of high voltage-activated (HVA) calcium (Ca2+) currents in freshly isolated striatal medium spiny neurons (MSNs) from rodent models of both idiopathic and familial forms of Parkinson's disease (PD). MSNs were recorded from reserpine-treated and 6-hydroxydopamine (6-OHDA)-lesioned rats, and from DJ-1 and PINK1 (PTEN induced kinase 1) knockout (-/-) mice. Our analysis showed no significant changes in total HVA Ca2+ current. However, we recorded a net increase in the L-type fraction of HVA Ca2+ current in dopamine-depleted rats, and of both N- and P-type components in DJ-1-/- mice, whereas no significant change in Ca2+ current profile was observed in PINK1-/- mice. Dopamine modulates HVA Ca2+ channels in MSNs, thus we also analyzed the effect of D1 and D2 receptor activation. The effect of the D1 receptor agonist SKF 83822 on Ca2+ current was not significantly different among MSNs from control animals or PD models. However, in both dopamine-depleted rats and DJ-1-/- mice the D2 receptor agonist quinpirole inhibited a greater fraction of HVA Ca2+ current than in the respective controls. Conversely, in MSNs from PINK1-/- mice we did not observe alterations in the effect of D2 receptor activation. Additionally, in both reserpine-treated and 6-OHDA-lesioned rats, the effect of quinpirole was occluded by the selective L-type Ca2+ channel blocker nifedipine, while in DJ-1-/- mice it was mostly occluded by ω-conotoxin GVIA, blocker of N-type channels. These results demonstrate that both dopamine depletion and DJ-1 deletion induce a rearrangement in the HVA Ca2+ channel profile, specifically involving those channels that are selectively modulated by D2 receptors.
  Neuroscience 12/2010; 177:240-51. · 3.38 Impact Factor
• Article: Metabotropic glutamate receptor subtype 4 selectively modulates both glutamate and GABA transmission in the striatum: implications for Parkinson's disease treatment.

  Dario Cuomo, Giuseppina Martella, Emanuela Barabino, Paola Platania, Daniela Vita, Graziella Madeo, Chelliah Selvam, Cyril Goudet, Nadia Oueslati, Jean-Philippe Pin, Francine Acher, Antonio Pisani, Corinne Beurrier, Christophe Melon, Lydia Kerkerian-Le Goff, Paolo Gubellini
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  ABSTRACT: Alterations of striatal synaptic transmission have been associated with several motor disorders involving the basal ganglia, such as Parkinson's disease. For this reason, we investigated the role of group-III metabotropic glutamate (mGlu) receptors in regulating synaptic transmission in the striatum by electrophysiological recordings and by using our novel orthosteric agonist (3S)-3-[(3-amino-3-carboxypropyl(hydroxy)phosphinyl)-hydroxymethyl]-5-nitrothiophene (LSP1-3081) and l-2-amino-4-phosphonobutanoate (L-AP4). Here, we show that both drugs dose-dependently reduced glutamate- and GABA-mediated post-synaptic potentials, and increased the paired-pulse ratio. Moreover, they decreased the frequency, but not the amplitude, of glutamate and GABA spontaneous and miniature post-synaptic currents. Their inhibitory effect was abolished by (RS)-alpha-cyclopropyl-4-phosphonophenylglycine and was lost in slices from mGlu4 knock-out mice. Furthermore, (S)-3,4-dicarboxyphenylglycine did not affect glutamate and GABA transmission. Finally, intrastriatal LSP1-3081 or L-AP4 injection improved akinesia measured by the cylinder test. These results demonstrate that mGlu4 receptor selectively modulates striatal glutamate and GABA synaptic transmission, suggesting that it could represent an interesting target for selective pharmacological intervention in movement disorders involving basal ganglia circuitry.
  Journal of Neurochemistry 06/2009; 109(4):1096-105. · 4.06 Impact Factor