3-mercaptopropionic acid-induced seizures decrease NR2B expression in Purkinje cells: Cyclopentyladenosine effect

Inhibitory mechanism of cerebellum epileptic activity can be involved depending on the intensity and frequency of seizure convulsions. N-methyl-D-aspartate receptors (NMDARs) play key roles in excitatory synaptic transmission and have been implicated in neurological disorders: in cerebellum, they have specific characteristics. NMDARs are heteromeric complexes, and the expression of functional receptors in mammalian cells requires the subunit NR1 (essential) and one NR2 subtype of the four isoforms: NR2A-NR2D. In mature Purkinje cells, the combination of NR1 with NR2B subunits forms functional NMDARs; NR2B subunit may be altered in exocitotoxic events. Cyclopentyladenosine (CPA), an adenosine analogue, administered to rats, for one or more days, increases seizure threshold induced by the convulsant drug 3-mercaptopropionic acid (MP). In this study, we focused on the expression of NR2B in cerebellum after repetitive seizures induced by MP and the effect of adenosine analogue CPA administered alone or previous to MP (CPA + MP). A significant decrease in NR2B in the whole cerebellum was observed after MP and CPA administration with a tendency to recover to normal values in the combined treatment of CPA administered 30 min before MP by Western blot assay. In immunohistochemical studies, NR2B expression was observed and analysed in Purkinje cells. NR2B expression was decreased after MP (55%) and CPA (12%) administration, and CPA injected 30 min before MP led to 28% reduction in Purkinje cells. These results could be related to Purkinje cell damage or alternatively to avoid the excitotoxic effect. Results recorded after CPA + MP treatment seemed involved in decreasing the convulsant MP effect.Fil: Girardi, Elena Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Auzmendi, Jerónimo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Charó, Nancy Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Gori, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Castro, Marcelo Fidel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE): Is it related with SUDEP?

Patients with refractory epilepsy (RE) have increased risk of Sudden Unexpected Death in Epilepsy (SUDEP), where acute and fatal heart failure is suspected. High seizure frequency, polypharmacy, changes in dosing, persistent low AED levels or poor adherence to therapy are the greatest risk factors of SUDEP and are also features observed in RE. We evaluated the progressive P-gp overexpression in heart, related with the development of fatal status epilepticus (FSE) after experimental repetitive seizures (ERS). Male Wistar rats (180–230g) were daily injected (i.p) with Pentylenetetrazole (PTZ; 45mg/kg; n=18) or saline (Controls; n=6). Severity of seizures was recorded. Four PTZ-treated rats were sacrificed at 4th-7th day respectively. Ten remaining rats, underwent same treatment until develop fatal status epilepticus (FSE). Brains and hearts were studied by immunofluorecent method for P-glycoptrotein (P-gp) expression. Seizures were observed each day of PTZ treatment, associated with a progressive P-gp overexpression in heart and FSE at 9th day. Using the same PTZ model, we previously demonstrated that progressive brain P-gp overexpression contributes to cell membrane depolarization of hippocampus and neocortex. These are the first evidences showing that ERS induces a simultaneous and progressive P-gp overexpression in brain and heart associated with FSE, and suggests a role for this pattern expression of P-gp as risk factor for death during SE. The simultaneous and spontaneous death of all animals during SE observed only at day 9th, suggest that a higher P-gp overexpression in cardiomyocytes could play a role in SUDEP, however, because it is only a study descriptive, further researches are needed to confirm this hypothesis.Fil: Auzmendi, Jerónimo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Merelli, Amalia Margarita. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Girardi, Elena Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Orozco Suárez, Sandra. Centro Médico Nacional Siglo XXI; MéxicoFil: Rocha Arrieta, Luisa Lilia. Centro de Investigación y de Estudios Avanzados. Departamento de Farmacobiología; MéxicoFil: Lazarowski, Alberto Jorge. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Fundación Investigar; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

CB1 Cannabinoid Receptor is a Target for Neuroprotection in Light Induced Retinal Degeneration

In the last few years, an increasing interest in the neuroprotective effect of cannabinoidshas taken place. The aim of the present work was to study the effects of modulatingcannabinoid receptor 1 (CB1) in the context of light induced retinal degeneration (LIRD),using an animal model that resembles many characteristics of human age-related maculardegeneration (AMD) and other degenerative diseases of the outer retina. Sprague Dawleyrats (n = 28) were intravitreally injected in the right eye with either a CB1 agonist (ACEA), oran antagonist (AM251). Contralateral eyes were injected with respective vehicles ascontrols. Then, rats were subjected to continuous illumination (12,000 lux) for 24 h.Retinas from 28 animals were processed by GFAP-immunohistochemistry (IHC),TUNEL technique, Western blotting (WB), or qRT-PCR. ACEA-treated retinas showeda significantly lower number of apoptotic nuclei in the outer nuclear layer (ONL), lower levelsof activated Caspase-3 by WB, and lower levels of glial reactivity by both GFAP-IHC andWB. qRT-PCR revealed that ACEA significantly decreased the expression of Bcl-2 andCYP1A1. Conversely, AM251-treated retinas showed a higher number of apoptotic nucleiin the ONL, higher levels of activated Caspase-3 by WB, and higher levels of glial reactivityas determined by GFAP-IHC and WB. AM251 increased the expression of Bcl-2, Bad,Bax, Aryl hydrocarbon Receptor (AhR), GFAP, and TNFα. In summary, the stimulation ofthe CB1 receptor, previous to the start of the pathogenic process, improved the survival ofphotoreceptors exposed to LIRD. The modulation of CB1 activity may be used as aneuroprotective strategy in retinal degeneration and deserves further studiesFil: Soliño, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Larráyoz, Ignacio M.. Center For Biomedical Research Of La Rioja; EspañaFil: Lopez, Ester Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Rey Funes, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Bareiro, Nidia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Girardi, Elena Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Caltana, Laura Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Brusco, Herminia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Martinez, Alfredo. Center For Biomedical Research Of La Rioja; EspañaFil: López, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20

3-Mercaptopropionic acid-induced repetitive seizures increase GluN2A expression in rat hippocampus: a potential neuroprotective role of cyclopentyladenosine

The N-methyl-d-aspartate receptor (NMDAR) is involved in synaptic plasticity, learning, memory, and neurological diseases like epilepsy and it is the major mediator of excitotoxicity. Functional NMDARs in the mature brain are heteromeric complexes composed of different subunits: GluN1 and GluN2. There are four different GluN2 subunits (A–D) and each of them critically determines the pharmacological and electrophysiological properties of NMDARs. GluN1 is ubiquitously expressed in the central nervous system while the highest GluN2A expression is in the hippocampus. Adenosine, an endogenous anticonvulsant, is a neuromodulator with a critical role in the regulation of neuronal activity, mediating its effect on specific receptors, among which adenosine A1 receptor is highly expressed in the hippocampus. In the present work hippocampal GluN2A expression after the convulsant drug 3-mercaptopropionic acid (MP) induced seizures and the effect of cyclopentyladenosine (CPA) given alone or prior to MP (CPA + MP) in an acute or repetitive experimental model was studied. CPA administered to rats for one or 4 days increases seizure threshold induced by MP. After one administration of MP, no significant difference in GluN2A expression was observed in CPA and CPA + MP by Western blot, although immunohistochemistry revealed an increase in CA2/3 area. However, repetitive MP administration during 4 days showed a significant increase of GluN2A expression, and the repetitive administration of CPA 30 min prior to MP caused a significant decrease of GluN2A expression with respect to MP treatment, returning to control levels. These results show that GluN2A subunit is involved in repetitive MP-induced seizures, while CPA administration displays a protective effect against it.Fil: Gori, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Girardi, Elena Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; Argentin

ATTIVAMENTE: Toccare e Contare per Imparare la matematica

Presentiamo un progetto di potenziamento rivolto a bambini della scuola dell’infanzia (4-5 anni) e intende favorire lo sviluppo di tre abilità che la ricerca in neuroscienze ritiene siano alla base delle abilità numeriche: abilità motorie fini, gnosia digitale, e subitizing. Viene usato un protocollo di potenziamento di queste abilità che prevede l’uso di 3 applicativi multi-touch per iPad: un applicativo richiede l’appoggio di un numero di dita corrispondenti a punti su coccinelle, un secondo applicativo propone percorsi che i bambini dovranno tracciare con dita diverse su richiesta dell’educatore, e il terzo applicativo chiede di riconoscere velocemente piccole numerosità di oggetti sullo schermo e di appoggiare simultaneamente il numero corrispondente di dita. Il protocollo è stato proposto a circa 200 bambini. Verrà presentato il protocollo e discussi i risultati preliminari dei pre- e post- test in relazione alle abilità acquisite e potenziate. Il progetto è realizzato grazie al contributo della Fondazione Cassa di Risparmio di Padova e Rovigo

Differential expression of cerebellar metabotropic glutamate receptors mGLUR2/3 and mGLUR4a after the administration of a convulsant drug and the adenosine analogue cyclopentyladenosine

Metabotropic glutamate receptors (mGluR) play a role in synaptic transmission, neuronal modulation and plasticity but their action in epileptic activity is still controversial. On the other hand adenosine acts as a neuromodulator with endogenous anticonvulsive properties. Since cerebellum from epileptic patients has shown neuronal damage, sometimes associated with Purkinje cells loss, we have explored the effect of repetitive seizures on two types of mGluR in the cerebellum. Seizures were induced by the convulsant drug 3-mercaptopropionic acid (MP) and the effect of the adenosine analogue cyclopentyladenosine (CPA) alone or before MP administration (CPA+MP) were also evaluated. The expression of the receptors subtypes 2/3 (mGluR2/3) and 4a (mGluR4a) was assessed by immunocitochemistry. Granular cell layer was labeled with mGluR2/3 antibody and increased immunoreactivity was observed after MP (60%), CPA (53%) and CPA + MP (85%) treatments. Control cerebellum slices showed mGluR4a reactivity around Purkinje cells, while MP, CPA and CPA+MP treatment decreased this immunostaining. Repetitive administration of MP and CPA induces an increased cerebellar mGluR2/3 and a decreased mGluR4a immunostaining, suggesting a distinct participation of both receptors that may be related to the type of cell involved. A protective action and /or an apoptotic effect may not be discarded. CPA repetitive administration although increase seizure latency, cannot prevent seizure activity.Fil: Girardi, Elena Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Canitrot, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: González, Nélida Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Coirini, Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin