IRCCS Neuromed Pozzilli

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IRCCS Neuromed Pozzilli

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Squitieri F.,IRCCS Neuromed Pozzilli | Sanchez-Castaneda C.,IRCCS Santa Lucia Foundation | Elifani F.,IRCCS Neuromed Pozzilli | Griguoli A.,IRCCS Neuromed Pozzilli | And 4 more authors.
Cerebral cortex (New York, N.Y. : 1991) | Year: 2015

Huntington's disease (HD) is characterized by progressive motor impairment. Therefore, the connectivity of the corticospinal tract (CST), which is the main white matter (WM) pathway that conducts motor impulses from the primary motor cortex to the spinal cord, merits particular attention. WM abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using magnetic resonance imaging (MRI). In the present study, we examined CST microstructure using diffusion tensor imaging (DTI)-based tractography in 30-direction DTI data collected from 100 subjects: Pre-HD subjects (n = 25), HD patients (n = 25) and control subjects (n = 50), and T2*-weighted (iron sensitive) imaging. Results show decreased fractional anisotropy (FA) and increased axial (AD), and radial diffusivity (RD) in the bilateral CST of HD patients. Pre-HD subjects had elevated iron in the left CST, regionally localized between the brainstem and thalamus. CAG repeat length in conjunction with age, as well as motor (UHDRS) assessment were correlated with CST FA, AD, and RD both in Pre-HD and HD. In the presymptomatic phase, increased iron in the inferior portion supports the "dying back" hypothesis that axonal damage advances in a retrograde fashion. Furthermore, early iron alteration may cause a high level of toxicity, which may contribute to further damage. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.


Missori P.,University of Rome La Sapienza | Coppola G.,Gb Bietti Eye Foundation Irccs | Paolini S.,University of Perugia | Pierelli F.,IRCCS Neuromed Pozzilli | And 2 more authors.
Journal of Clinical Neuroscience | Year: 2012

The lumbar tap test as a diagnostic and therapeutic procedure in idiopathic normal pressure hydrocephalus is used widely. Complications from lumbar punctures are rare. We report a man who underwent a tap-test for secondary normal pressure hydrocephalus, and after clinical improvement, suffered a fatal intraparenchymal brain haemorrhage three days later. © 2012 Elsevier Ltd. All rights reserved.


Antonelli M.,University of Rome La Sapienza | Hasselblatt M.,University of Munster | Haberler C.,Medical University of Vienna | Di Giannatale A.,Pediatric Hospital Giannina Gaslini | And 7 more authors.
Brain Pathology | Year: 2011

Recent gene expression microarray analyses have indicated that claudin-6 is specifically expressed in atypical teratoid rhabdoid tumors (AT/RTs), suggesting a role as a positive diagnostic marker in addition to SMARCB1 (INI1) loss, which is encountered in the majority of AT/RTs. In order to investigate the potential of claudin-6 as a diagnostic marker, expression was investigated in 59 AT/RTs and 60 other primary central nervous system (CNS) tumors, including primitive neuroectodermal tumors, medulloblastomas, choroid plexus tumors, and both pediatric and adult low- and high-grade gliomas using immunohistochemistry. Claudin-6 was expressed in 17/59 AT/RTs (29%), but also in a variety of other primary CNS tumors, including 60% of medulloblastomas and 21% of malignant gliomas. Even though high staining scores (2+ or 3+) were more often encountered in AT/RTs (Chi-square 4.177; P = 0.041), the overall frequency of claudin-6 staining was not significantly higher in AT/RTs as compared with the other tumors (17/59 vs. 16/60; Chi-square = 0.328; P = 0.567). In a subgroup of 43 AT/RT patients, of which follow-up data were available, claudin-6 expression did not show any correlation with survival. In conclusion, claudin-6 immunohistochemistry is of limited sensitivity and specificity for the diagnosis of AT/RT and does not correlate with clinical behavior. © 2011 International Society of Neuropathology.


Antonelli M.,University of Rome La Sapienza | Massimino M.,Fondazione IRCCS Instituto Nazionale dei Tumori | Morra I.,Hospital Regina Margherita | Garre M.L.,Hospital Giannina Gaslini | And 4 more authors.
Neuropathology | Year: 2012

The Ras signaling pathway, consisting of mitogen-activated protein kinase (MAPK) and PI3K/AKT signaling, is a prominent oncogenic pathways in adult diffuse gliomas, but few studies have evaluated such pathways in pediatric malignant gliomas. We investigated by immunohistochemistry MAPK and AKT signaling in a series of 28 pediatric high-grade gliomas (WHO grade III and IV). We sought a possible association of phospho-ERK (p-ERK) and phospho-AKT (p-AKT) with expression of other proteins involved in the Ras pathway, that is, YKL40, epidermal growth factor receptor (EGFR), EGFR vIII and c-Met. Moreover we correlated the expression of p-ERK and p-AKT with prognosis. No cases showed expression for c-Met and EGFR, and only one case was positive for EGFR vIII. YKL-40 protein was expressed in 43% of cases. We detected expression of p-ERK and p-AKT in 61% and 57%, respectively, of pediatric high grade gliomas. Statistical analysis comparing the two groups in term of high and low p-ERK and p-AKT expression showed a trend toward worse overall survival in patients with high expression of p-AKT. The activation of ERK and AKT suggest a possible role of this protein in inducing activation of the Ras signaling pathway in pediatric high-grade gliomas. Moreover high levels of p-AKT are associated with worse overall survival. © 2011 Japanese Society of Neuropathology.


Cantafora E.,University of Pisa | Giorgi F.S.,University of Pisa | Frenzilli G.,University of Pisa | Scarcelli V.,University of Pisa | And 5 more authors.
Journal of Neural Transmission | Year: 2014

We induced brief secondarily generalized seizures of limbic origin in Sprague-Dawley rats by bicuculline microinfusion into the anterior piriform cortex. After 1 h or 5 days we performed comet assay, a sensitive marker for DNA damage, within entorhinal cortex, hippocampus (limbic areas recruited by seizure spreading) and striatum (which is not recruited). DNA damage occurred selectively in the ipsilateral entorhinal cortex and hippocampus at 1 h, but not at 5 days. These data shed new light on molecular genetics as a marker during limbic seizures, the most common in epileptic patients. © 2014, Springer-Verlag Wien.


Arcella A.,I.R.C.C.S. Neuromed Pozzilli | Biagioni F.,I.R.C.C.S. Neuromed Pozzilli | Antonietta Oliva M.,I.R.C.C.S. Neuromed Pozzilli | Bucci D.,I.R.C.C.S. Neuromed Pozzilli | And 9 more authors.
Brain Research | Year: 2013

The molecular target of rapamycin (mTOR) is up-regulated in glioblastoma (GBM) and this is associated with the rate of cell growth, stem cell proliferation and disease relapse. Rapamycin is a powerful mTOR inhibitor and strong autophagy inducer. Previous studies analyzed the effects of rapamycin in GBM cell lines. However, to our knowledge, no experiment was carried out to evaluate the effects of rapamycin neither in primary cells derived from GBM patients nor in vivo in brain GBM xenograft. These data are critical to get a deeper insight into the effects of such adjuvant therapy in GBM patients. In the present study, various doses of rapamycin were tested in primary cell cultures from GBM patients. These effects were compared with that obtained by the same doses of rapamycin in GBM cell lines (U87Mg). The effects of rapamycin were also evaluated in vivo, in brain tumors developed from mouse xenografts. Rapamycin, starting at the dose of 10 nm inhibited cell growth both in U87Mg cell line and primary cell cultures derived from various GBM patients. When administered in vivo to brain xenografts in nude mice rapamycin almost doubled the survival time of mice and inhibited by more than 95% of tumor volume. © 2012 Elsevier B.V.


Antonelli M.,University of Rome La Sapienza | Caltabiano R.,University of Catania | Chiappetta C.,University of Rome La Sapienza | Oliva M.A.,IRCCS Neuromed Pozzilli | And 2 more authors.
Neuropathology | Year: 2011

Peripheral primitive neuroectodermal tumor/Ewing's sarcoma (ES) (pPNET/ES) of intracranial origin are very rare. These tumors are characterized by specific translocations involving a gene on chromosome 22q12, the most common being t(11;22) (q24;q12). We report a case of 37-year-old man with pPNET/ES arising in the meninges and bearing the rare translocation t(21;22) (q22;q12). The tumor was composed of sheets and nests of monotonous small cells with round to oval nuclei, finely dispersed chromatin, small nucleolus and scant cytoplasm. We discuss the importance of the differential diagnosis with central primitive neuroectodermal tumors (cPNET). © 2011 Japanese Society of Neuropathology.


PubMed | I.R.C.C.S. Neuromed Pozzilli
Type: | Journal: Brain research | Year: 2013

The molecular target of rapamycin (mTOR) is up-regulated in glioblastoma (GBM) and this is associated with the rate of cell growth, stem cell proliferation and disease relapse. Rapamycin is a powerful mTOR inhibitor and strong autophagy inducer. Previous studies analyzed the effects of rapamycin in GBM cell lines. However, to our knowledge, no experiment was carried out to evaluate the effects of rapamycin neither in primary cells derived from GBM patients nor in vivo in brain GBM xenograft. These data are critical to get a deeper insight into the effects of such adjuvant therapy in GBM patients. In the present study, various doses of rapamycin were tested in primary cell cultures from GBM patients. These effects were compared with that obtained by the same doses of rapamycin in GBM cell lines (U87Mg). The effects of rapamycin were also evaluated in vivo, in brain tumors developed from mouse xenografts. Rapamycin, starting at the dose of 10nm inhibited cell growth both in U87Mg cell line and primary cell cultures derived from various GBM patients. When administered in vivo to brain xenografts in nude mice rapamycin almost doubled the survival time of mice and inhibited by more than 95% of tumor volume.


PubMed | University of Rome Tor Vergata, IRCCS Neuromed Pozzilli and University of PisaPisa
Type: | Journal: Frontiers in neuroscience | Year: 2016

Mammalian retromers play a critical role in protein trans-membrane sorting from endosome to the trans-Golgi network (TGN). Recently, retromer alterations have been related to the onset of Parkinsons Disease (PD) since the variant p.Asp620Asn in VPS35 (Vacuolar Protein Sorting 35) was identified as a cause of late onset PD. This variant causes a primary defect in endosomal trafficking and retromers formation. Other mutations in VPS genes have been reported in both sporadic and familial PD. These mutations are less defined. Understanding the specific prevalence of all VPS gene mutations is key to understand the relevance of retromers impairment in the onset of PD. A number of PD-related mutations despite affecting different biochemical systems (autophagy, mitophagy, proteasome, endosomes, protein folding), all converge in producing an impairment in cell clearance. This may explain how genetic predispositions to PD may derive from slightly deleterious VPS mutations when combined with environmental agents overwhelming the clearance of the cell. This manuscript reviews genetic data produced in the last 5 years to re-define the actual prevalence of VPS gene mutations in the onset of PD. The prevalence of p.Asp620Asn mutation in VPS35 is 0.286 of familial PD. This increases up to 0.548 when considering mutations affecting all VPS genes. This configures mutations in VPS genes as the second most frequent autosomal dominant PD genotype. This high prevalence, joined with increased awareness of the role played by retromers in the neurobiology of PD, suggests environmentally-induced VPS alterations as crucial in the genesis of PD.

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