lunedì 21 novembre 2016

Scopus news

Makovac, E., Cercignani, M., Serra, L., Torso, M., Spanò, B., Petrucci, S., Ricciardi, L., Ginevrino, M., Caltagirone, C., Bentivoglio, A.R., Valente, E.M., Bozzali, M.
Brain connectivity changes in autosomal recessive Parkinson disease: A model for the sporadic form
(2016) PLoS ONE, 11 (10), art. no. e0163980, .
DOI: 10.1371/journal.pone.0163980
AFFILIATIONS: Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; 
Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Falmer, Brighton, United Kingdom; 
IRCCS Casa Sollievo della Sofferenza, CSS-Mendel laboratory, San Giovanni Rotondo, Italy; 
Dept. of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy; 
Sobell Dept. of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, United Kingdom; 
Dept. of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; 
Dept. of Neuroscience, University of Rome 'Tor Vergata', Rome, Italy; 
Dept. of Neurosciences, Catholic University, Rome, Italy; 
Section of Neurosciences, Dept. of Medicine and Surgery, University of Salerno, Salerno, Italy
ABSTRACT: Biallelic genetic mutations in the Park2 and PINK1 genes are frequent causes of autosomal recessive PD. Carriers of single heterozygous mutations may manifest subtle signs of disease, thus providing a unique model of preclinical PD. One emerging hypothesis suggests that non-motor symptom of PD, such as cognitive impairment may be due to a distributed functional disruption of various neuronal circuits. Using resting-state functional MRI (RSfMRI), we tested the hypothesis that abnormal connectivity within and between brain networks may account for the patients' cognitive status. Eight homozygous and 12 heterozygous carriers of either PINK1 or Park2 mutation and 22 healthy controls underwent RSfMRI and cognitive assessment. RS-fMRI data underwent independent component analysis to identify five networks of interest: default-mode network, salience network, executive network, right and left fronto-parietal networks. Functional connectivity within and between each network was assessed and compared between groups. All mutation carriers were cognitively impaired, with the homozygous group reporting a more prominent impairment in visuo-spatial working memory. Changes in functional connectivity were evident within all networks between homozygous carriers and controls. Also heterozygotes reported areas of reduced connectivity when compared to controls within two networks. Additionally, increased inter-network connectivity was observed in both groups of mutation carriers, which correlated with their spatial working memory performance, and could thus be interpreted as compensatory. We conclude that both homozygous and heterozygous carriers exhibit pathophysiological changes unveiled by RS-fMRI, which can account for the presence/severity of cognitive symptoms. Copyright © 2016 Makovac et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Scopus news

Krashia, P., Ledonne, A., Nobili, A., Cordella, A., Errico, F., Usiello, A., D'Amelio, M., Mercuri, N.B., Guatteo, E., Carunchio, I.
Persistent elevation of D-Aspartate enhances NMDA receptor-mediated responses in mouse substantia nigra pars compacta dopamine neurons
(2016) Neuropharmacology, 103, pp. 69-78.

DOI: 10.1016/j.neuropharm.2015.12.013
AFFILIATIONS: Department of Experimental Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; 
Department of Medicine, Unit of Molecular Neurosciences, University Campus-Biomedico, Rome, Italy; 
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 
Ceinge Biotecnologie Avanzate, Naples, Italy; 
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy; 
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples (SUN), Caserta, Italy
ABSTRACT: Dopamine neurons in the substantia nigra pars compacta regulate not only motor but also cognitive functions. NMDA receptors play a crucial role in modulating the activity of these cells. Considering that the amino-acid D-Aspartate has been recently shown to be an endogenous NMDA receptor agonist, the aim of the present study was to examine the effects of D-Aspartate on the functional properties of nigral dopamine neurons. We compared the electrophysiological actions of D-Aspartate in control and D-aspartate oxidase gene (Ddo-/-) knock-out mice that show a concomitant increase in brain D-Aspartate levels, improved synaptic plasticity and cognition. Finally, we analyzed the effects of L-Aspartate, a known dopamine neuron endogenous agonist in control and Ddo-/- mice. We show that D- and L-Aspartate excite dopamine neurons by activating NMDA, AMPA and metabotropic glutamate receptors. Ddo deletion did not alter the intrinsic properties or dopamine sensitivity of dopamine neurons. However, NMDA-induced currents were enhanced and membrane levels of the NMDA receptor GluN1 and GluN2A subunits were increased. Inhibition of excitatory amino-acid transporters caused a marked potentiation of D-Aspartate, but not L-Aspartate currents, in Ddo-/- neurons. This is the first study to show the actions of D-Aspartate on midbrain dopamine neurons, activating not only NMDA but also non-NMDA receptors. Our data suggest that dopamine neurons, under conditions of high D-Aspartate levels, build a protective uptake mechanism to compensate for increased NMDA receptor numbers and cell hyper-excitation, which could prevent the consequent hyper-dopaminergia in target zones that can lead to neuronal degeneration, motor and cognitive alterations. © 2015 Elsevier Ltd. All rights reserved.
CORRESPONDENCE ADDRESS: Guatteo, E.; Department of Experimental Neurology, IRCCS Santa Lucia FoundationItaly; email:

mercoledì 16 novembre 2016

Seminario su "Infiammazione ed epilessia: meccanismi e conseguenze"

Mercoledi 23 novembre 2016 alle ore 16 

Policlinico universitario Federico II - via Pansini 5,  Aula grande dell’Edificio 11 di Pediatria 

 seminario di Annamaria Vezzani:

Infiammazione ed epilessia: meccanismi e conseguenze 

Annamaria Vezzani è Direttore del Laboratorio di Neurologia Sperimentale dell'Istituto di Ricerche Farmacologiche Mario Negri di Milano. La sua formazione si è svolta all'Università del Maryland a Baltimora, al Karolinska Institute di Stoccolma e all'Albert Einstein College of Medicine nel laboratorio dedicato a Developmental Epilepsy.
La sua principale linea di ricerca è tesa allo studio dei meccanismi biochimici e molecolari coinvolti nella patogenesi delle crisi epilettiche e nella epilettogenesi in modelli sperimentali. Le sue pubblicazioni contano più di 160 lavori originali e numerosi capitoli di libri (H-index 57). E' stata designata come Chair della Commissione sulla Neurobiologia della ILAE (International League against Epilepsy) che promuove iniziative per migliorare la ricerca traslazionale in epilettologia. Ha ricevuto il Research Recognition Award for Translational research dall'American Epilepsy Society.