GATTA , Elena

GABA-activated chloride currents were studied in cerebellar granule cells put in culture from neonatal rats. As previously described, 10 µM GABA perfusion of these cells recorded by whole cell patch-clamp elicits chloride currents displaying a peak and a steady-state component. The two components were studied in the presence of 1 mM...

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GABAA receptor mediated inhibition plays an important role in modulating the input/output dynamics of cerebellum. A characteristic of cerebellar GABAA receptors is the presence in cerebellar granule cells of subunits such as a6 and d which give insensitivity to classical benzodiazepines. In fact, cerebellar GABAA receptors have generally been...

Various new 1,5-benzodiazepine compounds were synthesized and tested for their biological activity in terms of effects on GABA(A) receptors of rat cerebellar granules in culture. Their effects were compared to those of a 1,4-benzodiazepine agonist, flunitrazepam and the already known 1,5-benzodiazepine antiepileptic clobazam. The effects were...

In previous work our group described the synthesis and the activity on rat cerebellum granule cell GABAA receptors of new 1,5-benzodiazepine compounds. Here we are describing the synthesis of new triazolobenzodiazepines (mainly 1,5-benzodiazepine derivatives) and the evaluation of their biological activity in terms of effects on those GABAA...

The effects of a classical 1,4-benzodiazepine agonist, such as diazepam, its catabolite N-desmethyl-diazepam (nordiazepam), and 1,5-benzodiazepines such as clobazam and RL 214 (a triazolobenzodiazepine previously synthesized in our labs) were evaluated on native GABA(A) receptors of cerebellar granule cells in culture. The parameter studied was...

Glia over-stimulation associates with amyloid deposition contributing to the progression of central nervous system neurodegenerative disorders. Here we analyze the molecular mechanisms mediating microglia-dependent neurotoxicity induced by prion protein (PrP)90–231, an amyloidogenic polypeptide corresponding to the protease-resistant portion of...

Prion diseases recognize, as a unique molecular trait, the misfolding of CNS-enriched prion protein (PrP(C)) into an aberrant isoform (PrP(Sc)). In this work, we characterize the in vitro toxicity of amino-terminally truncated recombinant PrP fragment (amino acids 90-231, PrP90-231), on rat cerebellar granule neurons (CGN), focusing on...

Herein, we tested in a model of generalized reflex epilepsy in mice different 1,4-benzodiazepines and 1,5-benzodiazepines with agonistic activity at the GABAA receptor population contributing to the peak component of the chloride current elicited by GABA in cerebellar granule cells (CGCs) in culture. The substances have all higher lipophilia...

A wide consensus based on robust experimental evidence indicates pyroglutamylated amyloid-β isoform (AβpE3-42) as one of the most neurotoxic peptides involved in the onset of Alzheimer's disease. Furthermore, AβpE3-42 co-oligomerized with excess of Aβ1-42, produces oligomers and aggregates that are structurally distinct and far more cytotoxic...

We tested the efficacy of novel cyclooxygenase 2 (COX-2) inhibitors in counteracting glia-driven neuroinflammation induced by the amyloidogenic prion protein fragment PrP90-231 or lipopolysaccharide (LPS). In search for molecules with higher efficacy than celecoxib, we focused our study on its 2,3-diaryl-1,3-thiazolidin-4-one analogues. As...

Activation of microglia is a central event in the atypical inflammatory response occurring during prion encephalopathies. We report that the prion protein fragment encompassing amino acids 90-231 (PrP90-231), a model of the neurotoxic activity of the pathogenic prion protein (PrP(Sc)), causes activation of both primary microglia cultures and N9...

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Alternative splicing generates protein isoforms that are conditionally or differentially expressed in specific tissues. Discovery of factors that control alternative splicing might clarify the molecular basis of biological and pathological processes. We found that IL1-α dependent upregulation of 38A, a small RNA polymerase III-transcribed...