Publications by authors named "Canolle B"

The treatment of negative symptoms (NS) in psychosis represents an urgent unmet medical need given the significant functional impairment it contributes to psychosis syndromes. The lack of progress in treating NS is impacted by the lack of known pathophysiology or associated quantitative biomarkers, which could provide tools for research. This current analysis investigated potential associations between NS and an extensive battery of behavioral and brain-based biomarkers in 932 psychosis probands from the B-SNIP database.

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Background: Traumatic brain injury (TBI) results in long-term neurological deficits, which may be mediated in part by pro-inflammatory responses in both the injured brain and the circulation. Inflammation may be involved in the subsequent development of neurodegenerative diseases and post-injury seizures. The p75 neurotrophin receptor (p75NTR) has multiple biological functions, affecting cell survival, apoptotic cell death, axonal growth, and degeneration in pathological conditions.

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The p75 neurotrophin receptor is important in multiple physiological actions including neuronal survival and neurite outgrowth during development, and after central nervous system injury. We have discovered a novel piperazine-derived compound, EVT901, which interferes with p75 neurotrophin receptor oligomerization through direct interaction with the first cysteine-rich domain of the extracellular region. Using ligand binding assays with cysteine-rich domains-fused p75 neurotrophin receptor, we confirmed that EVT901 interferes with oligomerization of full-length p75 neurotrophin receptor in a dose-dependent manner.

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Objectives: In the adult human brain, neurogenesis occurs in the SVZ and the dentate gyrus of the hippocampus, but it is still unclear whether persistent neural progenitor/stem cells are also present in other brain areas. The present work studies the possibility of obtaining neural progenitor/stem cells from the temporal lobe and investigates their potential to differentiate into neuronal cells.

Methods: Human biopsies from the temporal lobe of epileptic patients were used to isolate potential neural progenitors.

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At the glutamatergic synapse the neurotransmitter is removed from the synaptic cleft by high affinity amino acid transporters located on neurons (EAAC1) and astrocytes (GLAST and GLT1), and a coordinated action of these cells is necessary in order to regulate glutamate extracellular concentration. We show here that treatment of neuronal cultures with glial soluble factors (GCM) is associated with a redistribution of EAAC1 and GLAST to the cell membrane and we analysed the effect of membrane cholesterol depletion on this regulation. In enriched neuronal culture (90% neurons and 10% astrocytes), GCM treatment for 10 days increases EAAC1 and GLAST cell surface expression with no change in total expression.

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EAAC1/EAAT3 is a transporter of glutamate (Glu) present at the post-synaptic neuronal element, in opposition to the two other main transporters, GLAST/EAAT1 and GLT1/EAAT2, expressed at the excitatory amino acid (EAA) synapse by surrounding astrocytes. Although, in the adult, EAAC1/EAAT3 exhibits a rather low expression level and is considered to make a minor contribution to Glu removal from the synapse, its early expression during brain development, before the astrocytes are functional, suggests that such a neuronal transporter is involved in the developmental effects of EAA and, possibly, in the biosynthesis and trophic role of GABA, which is excitatory in nature in different brain regions during the earlier stages of brain development. This neuronal Glu transporter is considered to have a dual action as it is apparently involved in the neuronal uptake of cysteine, which acts as a key substrate for the synthesis of glutathione, a major anti-oxidant, because the neurones do not express the Xc(-) transport system in the mature brain.

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Background: The mechanisms underlying the neuroprotective effects of the immunosuppressant tacrolimus, observed in vivo, remain unclear. Here we quantify these effects in vitro, and evaluate the potential involvement of the glutamate and/or immunophilin FK506 binding protein 12 kDa in tacrolimus-induced neuroprotection.

Methods: Primary cultures of neurons and astrocytes from rat cerebral cortex were subjected to transient oxygen-glucose deprivation.

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This study described the involvement of short-term PKA, PKC or PI3K phosphorylation-mediated processes in the regulation of activity and trafficking of the excitatory amino acid transporters EAAC1, GLAST and GLT-1 endogenously expressed in neuron-enriched cultures. Glutamate uptake was dose-dependently decreased by inhibitors of protein kinase A (PKA), [N-[2-(p-bromocinnamylamino)-ethyl]-5-(isoquinolinesulfonamide)] (H89) or phosphatidylinositol 3-kinase (PI3K) (wortmannin), but not altered after protein kinase C (PKC) inhibition (staurosporine) or activation phorbol-12-myristate-13-acetate (PMA). Biotinylation and immunoblotting results (% of controls) showed that EAAC1 membrane expression was significantly decreased by H89 (71.

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A co-ordinated regulation between neurons and astrocytes is essential for the control of extracellular glutamate concentration. Here, we have investigated the influence of astrocytes and glia-derived cholesterol on the regulation of glutamate transport in primary neuronal cultures from rat embryonic cortices. Glutamate uptake rate and expression of the neuronal glutamate transporter EAAC1 were low when neurons were grown without astrocytes and neurons were unable to clear extracellular glutamate.

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