Alessandra Bergami - Academia.edu (original) (raw)

Papers by Alessandra Bergami

Gene Therapy, 2001

Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system ... more Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system (CNS) that might benefit from anti-inflammatory therapies. However, systemic delivery of anti-inflammatory drugs in MS patients has so far been disappointing, mostly due to the limited capacity of these molecules to enter the CNS. We injected into the cisterna magna (i.c.) of Biozzi AB/H mice affected by a relapsing-remitting form of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, a non-replicative herpes simplex virus (HSV) type-1-derived vector containing the interleukin (IL)-4 gene (d120:LacZ:IL-4). CNS delivery of the d120:LacZ:IL-4 vector, after EAE onset, induced the in situ production of IL-4 by CNS-resident cells facing the cerebrospinal fluid (CSF) spaces and reduced by 47% (P Ͻ 0.02) the disease-related deaths. Compared with mice treated with the control d120:LacZ vector, IL-4-treated mice also showed a shorter duration of the first EAE attack, a

by C. Bonetto, Stefano Torresani, Carla Cremonese, Paolo Scocco, Katia Santi, Veronica Marinelli, Renato Magnabosco, Spyridon Zotos, Ileana Boggian, enrico ceccato, Rosa Dall'Agnola, Raffaello Conti, Marta Zenari, Giovanni Austoni, Aldo Gatto, Anna Dominoni, Mauro Scabbio, Roberto Marchioro, Walter Paganelli, Maria Piscitelli, Gregorio Reggiani, Damiano Suzzi, Stefano Cenni, Glenda Marzola, Carla Leoni, Roberta Cellesi, Virginia Brambilla, Anita Montanari, M. Pellizzer, Silvia Azzali, Luca Bensi, Davide Cappellari, Nadia Campagnola, Laura Mairaghi, Sara Malak, Luca Mesiano, Manuela Soave, Natascia Brondino, Alessandra Bergami, Donatella Bolzon, Karin Furlato, Sara Garlassi, Alessandro Gavarini, Fabio Macchetti, Stefano Totaro, and Barbara Bianchi

TRIALS, 2012

Background: Multi-element interventions for first-episode psychosis (FEP) are promising, but have... more Background: Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services. Methods/Design: The Psychosis early Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a larger research program (Genetics, Endophenotypes and Treatment: Understanding early Psychosis -GET UP) which aims to compare, at 9 months, the effectiveness of a multi-component psychosocial intervention versus treatment as usual (TAU) in a large epidemiologically based cohort of patients with FEP and their family members recruited from all public community mental health centers (CMHCs) located in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster randomized controlled design. The randomized units (clusters) are the CMHCs, and the units of observation are the centers' patients and their family members. Patients in the experimental group will receive TAU plus: 1) cognitive behavioral therapy sessions, 2) psycho-educational sessions for family members, and 3) case management. Patient enrolment will take place over a 1-year period. Several psychopathological, psychological, functioning, and service use variables will be assessed at baseline and follow-up. The primary outcomes are: 1) change from baseline to follow-up in positive and negative symptoms' severity and subjective appraisal; 2) relapse occurrences between baseline and follow-up, that is, episodes resulting in admission and/or any case-note records of re-emergence of positive psychotic symptoms. The expected number of recruited patients is about 400, and that of relatives about 300.

Background: Acetylcholine receptor (AChR) from hu- man muscles is the antigen used currently in r... more Background: Acetylcholine receptor (AChR) from hu- man muscles is the antigen used currently in radioim- munoprecipitation assays (RIPAs) for the determination of anti-AChR antibodies in the diagnosis of myasthenia gravis (MG). Our aim was to develop and validate an ELISA using TE671 cells as the source of AChR. Methods: After TE671 cell homogenization, the crude AChR extract was used for

NeuroMolecular Medicine, 2014

During multiple sclerosis (MS) inflammatory attacks, and in subsequent clinical recovery phases, ... more During multiple sclerosis (MS) inflammatory attacks, and in subsequent clinical recovery phases, immune cells contribute to neuronal and oligodendroglial cell survival and tissue repair by secreting growth factors. Animal studies showed that growth factors also play a substantial role in regulating synaptic plasticity, and namely in long-term potentiation (LTP). LTP could drive clinical recovery in relapsing patients by restoring the excitability of denervated neurons. We recently reported that maintenance of synaptic plasticity reserve is crucial to contrast clinical deterioration in MS and that the platelet-derived growth factor (PDGF) may play a key role in its regulation. We also reported that a Hebbian form of LTP-like cortical plasticity, explored by paired associative stimulation (PAS), correlates with clinical recovery from a relapse in MS. Here, we explored the role of PDGF in clinical recovery and in adaptive neuroplasticity in relapsing-remitting MS (RR-MS) patients. We found a correlation between the cerebrospinal fluid (CSF) PDGF concentrations and the extent of clinical recovery after a relapse, as full recovery was more likely observed in patients with high PDGF concentrations and poor recovery in subjects with low PDGF levels. Consistently with the idea that PDGF-driven synaptic plasticity contributes to attenuate the clinical consequences of tissue damage in RR-MS, we also found a striking correlation between CSF levels of PDGF and the amplitude of LTP-like cortical plasticity explored by PAS. CSF levels of fibroblast growth factor, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor did not correlate with clinical recovery nor with measures of synaptic transmission and plasticity.

Naunyn-Schmiedeberg's Archives of Pharmacology, 1996

The effects of repeated subcutaneous (s.c) injections of dexfenfluramine (d-F; 10 mg/kg, twice da... more The effects of repeated subcutaneous (s.c) injections of dexfenfluramine (d-F; 10 mg/kg, twice daily, for 4 days) on the contents of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the brain were assessed in primates (cynomolgus and rhesus monkeys) and compared with the regional brain concentrations of unchanged drug and its active metabolite, dexnorfenfluramine (d-NF). This four-day, high-dose, regimen caused a large depletion of 5-HT (more than 95%) and of 5-HIAA (80-90%) in all brain areas studied (cortex, hippocampus, putamen, caudate nucleus and hypothalamus) 2 h after the last injection of d-F. Analysis of the plasma and brain contents of d-F and d-NF confirmed that both compounds were concentrated as in other species, in regions of the primate brain. However, d-NF was concentrated to a greater extent than d-F, and there were differences between the two primate species. Unlike in the rat brain, concentrations of d-NF greatly exceeded those of d-F in the primate brain suggesting that in these primates the d-NF may play a major role in the overall neurochemical response. The effects of d-F and d-NF on different in vitro parameters of serotoninergic neuronal function did not show appreciable differences between cynomolgus or rhesus monkeys when compared to rats, the ability of the two compounds to inhibit 5-HT reuptake, to enhance its release, and to affect the binding of [aH] -d-F or of [aH] -mesulergine (a ligand for 5-HT2c receptors) being similar. Kinetic differences in the disposition of d-F appear to have more relevance than biochemical effects in providing an explanation for the more marked brain depletion induced by d-F in primates than in rodents.

Nature, 2005

In degenerative disorders of the central nervous system (CNS), transplantation of neural multipot... more In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells 1,2 . Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model of chronic CNS inflammation, systemically injected adult syngeneic NPCs use constitutively activated integrins and functional chemokine receptors to selectively enter the inflamed CNS. These undifferentiated cells survive repeated episodes of CNS inflammation by accumulating within perivascular areas where reactive astrocytes, inflamed endothelial cells and encephalitogenic T cells produce neurogenic and gliogenic regulators. In perivascular CNS areas, surviving adult NPCs induce apoptosis of blood-borne CNS-infiltrating encephalitogenic T cells, thus protecting against chronic neural tissue loss as well as diseaserelated disability. These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection.

Journal of Neuroimmunology, 2000

Systemic administration of interferon (IFN)-b has been recently approved for the treatment of rel... more Systemic administration of interferon (IFN)-b has been recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The immunological mechanism by which IFN-b ameliorates MS is still partially unknown. We measured the number of blood 1 2 1 2 circulating CD4 , CD4 , CD8 , and CD8 T cells secreting IFN-g and IL-4 in 26 RRMS patients followed for up to 9 months of an 1 alternate day s.c. treatment with 8316 IU of IFN-b1b. Compared to pre-treatment values, a significant (P,0.05) reduction of CD4 , 2 1 2 1 2

Journal of Neuroimmunology, 2012

The aim of this study is to investigate the expression of P2X7R, IL-1beta and the ATP activity mo... more The aim of this study is to investigate the expression of P2X7R, IL-1beta and the ATP activity modulating ecto-apyrase CD39 on peripheral blood monocytes of MS patients and to observe the possible effects of Glatiramer Acetate (GA) on such expression. Twelve RR treatment-free MS patients were selected and peripheral blood monocytes were obtained. The expression of P2X7R, IL-1beta and CD39 on monocytes was investigated by qrt-PCR. The in vitro effects of GA on the expression of monocytes stimulated with BzATP (a potent P2X7R agonist)-were evaluated. Ten healthy donors (HDs) were similarly studied. Finally, 5 MS patients were given GA therapy and the monocytes obtained before treatment, after 3 and 12 months of GA treatment were similarly investigated. No differences were found in P2X7R, IL-1beta and CD39 expression between patients and controls. In MS Bz-ATP stimulated monocytes, GA pre-conditioning clearly downregulated P2X7R (p=0.003) but IL-1beta expression also showed a decreasing trend (p=0.07). Conversely, CD39 showed an increasing trend (p=0.07). Similar evidence was found in HDs. GA in vivo treatment induced a reduction in the expression that was clear for P2X7R and CD39 (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) but only not significant for IL-1beta after 12 months of treatment. Monocytes from both MS and control subjects express P2X7R, IL-1beta and CD39, and GA seems to interfere with such expression.

European Journal of Immunology, 2003

Invariant NKT (inv. NKT) cells co-express an invariant § g T cell receptor and the NK receptor NK... more Invariant NKT (inv. NKT) cells co-express an invariant § g T cell receptor and the NK receptor NK1.1 and, upon CD1d-restricted recognition of the glycosphingolipid antigen § -galactosyl ceramide ( § GalCer), secrete large amounts of regulatory cytokines. We investigated whether § GalCer-dependent activation of inv. NKT cells protects from experimental autoimmune encephalomyelitis (EAE), an immune-mediated disease of the central nervous system mimicking multiple sclerosis, induced in C57BL/6 mice by the myelin oligodendrocyte glycoprotein (MOG) encephalitogenic peptide aa 35-55. § GalCer was administered at the time of immunization s.c., mixed with complete Freund's adjuvant and MOG35-55 peptide, or administered i.p., diluted in PBS. EAE onset was delayed and disease severity was decreased only when § GalCer was s.c. administered. The protective effect of s.c. administration of § GalCer was associated with a markedly enhanced IFN-+ production by liverconfined inv. NKT cells which, in turn, suppressed Th1-cytokine production and fostered secretion of IL-10 from MOG35-55-specific T cells. In vivo neutralization of IFN-+ , but not IL-4, reversed the protective effect induced by s.c. administration of § GalCer, further confirming the critical regulatory role exerted by IFN-+ -producing inv. NKT cells. Our results indicate that § GalCer, properly administered, may elicit an inv. NKT-cell-mediated suppressive effect on the effector function of encephalitogenic T cells; this effect is able to ameliorate autoimmune demyelination.

Annals of Neurology, 2012

Microvesicles (MVs) have been indicated as important mediators of intercellular communication and... more Microvesicles (MVs) have been indicated as important mediators of intercellular communication and are emerging as new biomarkers of tissue damage. Our previous data indicate that reactive microglia/macrophages release MVs in vitro. The aim of the study was to evaluate whether MVs are released by microglia/macrophages in vivo and whether their number varies in brain inflammatory conditions, such as multiple sclerosis (MS). Electron and fluorescence microscopy and flow cytometry were used to detect myeloid MVs in the cerebrospinal fluid (CSF) of healthy controls, MS patients, and rodents affected by experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Myeloid MVs were detected in CSF of healthy controls. In relapsing and remitting EAE mice, the concentration of myeloid MVs in the CSF was significantly increased and closely associated with disease course. Analysis of MVs in the CSF of 28 relapsing patients and 28 patients with clinical isolated syndrome from 2 independent cohorts revealed higher levels of myeloid MVs than in 13 age-matched controls, indicating a clinical value of MVs as a companion tool to capture disease activity. Myeloid MVs were found to spread inflammatory signals both in vitro and in vivo at the site of administration; mice impaired in MV shedding were protected from EAE, suggesting a pathogenic role for MVs in the disease. Finally, FTY720, the first approved oral MS drug, significantly reduced the amount of MVs in the CSF of EAE-treated mice. These findings identify myeloid MVs as a marker and therapeutic target of brain inflammation.