Papers by Enrico Cherubini
Cells, 2022
GABA depolarizes and often excites immature neurons in all animal species and brain structures in... more GABA depolarizes and often excites immature neurons in all animal species and brain structures investigated due to a developmentally regulated reduction in intracellular chloride concentration ([Cl−]i) levels. The control of [Cl−]i levels is mediated by the chloride cotransporters NKCC1 and KCC2, the former usually importing chloride and the latter exporting it. The GABA polarity shift has been extensively validated in several experimental conditions using often the NKCC1 chloride importer antagonist bumetanide. In spite of an intrinsic heterogeneity, this shift is abolished in many experimental conditions associated with developmental disorders including autism, Rett syndrome, fragile X syndrome, or maternal immune activation. Using bumetanide, an EMA- and FDA-approved agent, many clinical trials have shown promising results with the expected side effects. Kaila et al. have repeatedly challenged these experimental and clinical observations. Here, we reply to the recent reviews by K...
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Frontiers in Cellular Neuroscience
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Revue d&'apos;Electroencéphalographie et de Neurophysiologie Clinique, 1973
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The Journal of Physiology, 1994
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The Journal of Physiology, 2001
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Neuroscience Letters, 1994
The inside out configuration of the patch-clamp technique was used to study single-channel anioni... more The inside out configuration of the patch-clamp technique was used to study single-channel anionic currents from purified hippocampal synaptosomes fused into liposomes to form giant proteoliposomes. At least six different anionic channels with unitary conductances of 22-150 pS were found. The most frequently observed was the 32-pS conductance channel. This was voltage-dependent; the open probability increased from 0.20 at -40 mV to 0.46 at 40 mV. This channel may be involved in the repolarization of nerve terminal membranes after an action potential, thus, limiting the duration of the spike and the transmitter release.
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Frontiers in Cellular Neuroscience
Epilepsy is a neurological disorder characterized by recurrent seizures, which result from excess... more Epilepsy is a neurological disorder characterized by recurrent seizures, which result from excessive, synchronous discharges of neurons in different brain areas. In about 30% of cases, epileptic discharges, which vary in their etiology and symptomatology, are difficult to treat with conventional drugs. Ferroptosis is a newly defined iron-dependent programmed cell death, characterized by excessive accumulation of lipid peroxides and reactive oxygen species. Evidence has been provided that ferroptosis is involved in epilepsy, and in particular in those forms resistant to drugs. Here, whole cell patch clamp recordings, in current and voltage clamp configurations, were performed from layer IV principal neurons in cortical slices obtained from adult mouse brain. Application of the ferroptosis inducer RAS-selective lethal 3 (RSL3) induced interictal epileptiform discharges which started at RSL3 concentrations of 2 μM and reached a plateau at 10 μM. This effect was not due to changes in ac...
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Neurotransmitters in Epilepsy, 1992
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Trends in Neurosciences, 1991
In the adult mammalian CNS, GABA is the main inhibitory transmitter. It inhibits neuronal firing ... more In the adult mammalian CNS, GABA is the main inhibitory transmitter. It inhibits neuronal firing by increasing a Cl- conductance. Bicuculline blocks this effect and induces interictal discharges. A different picture is present in neonatal hippocampal neurones, where synaptically released or exogenously applied GABA depolarizes and excites neuronal membranes--an effect that is due to a different Cl- gradient. In fact, during the early neonatal period, GABA acting on GABAA receptors provides most of the excitatory drive, whereas excitatory glutamatergic synapses are quiescent. It is suggested that during development GABA exerts mainly a trophic action through membrane depolarization and a rise in intracellular Ca2+.
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Frontiers in Cellular Neuroscience, 2020
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Frontiers in Psychiatry, 2019
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Brain Research, 1999
Binding studies were used to assess the changes in affinity and/or number of M1 muscarinic recept... more Binding studies were used to assess the changes in affinity and/or number of M1 muscarinic receptors in hippocampi from juvenile rats chronically deprived of NGF. NGF deprivation was obtained by implanting into right ventricle at postnatal day 2 (P2) hybrydoma cells secreting high levels of monoclonal antibodies against NGF (alphaD11). Parenteral myeloma cells (P3U) were used as controls. Competition experiments were used to characterise the [3H]-PNZ binding sites in membrane preparations of hippocampi from rats sacrificed at P15. [3H]-PNZ bound M1 receptors both in P3U and alphaD11 group as shown by displacing potency order of antagonists: TLZ=4-DAMP>PNZ>p-F-HHSiD>MTC. The deprivation of NGF for two weeks significantly increased the number of M1 receptors without changing the Ki values of antagonists with exception of methoctramine which showed an increase in affinity in alphaD11 group. Similar changes in binding parameters were already observed after the first week of anti-NGF treatment. In contrast, a treatment for a week with implant at postnatal day 15 failed to produce any changes in M1 binding parameters. These results provide further physiological evidence for developmentally regulated modulatory role of NGF in the cholinergic function in the hippocampus.
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European Journal of Neuroscience, 2010
We report gene profiling data on genomic processes underlying the progression towards recurrent s... more We report gene profiling data on genomic processes underlying the progression towards recurrent seizures after injection of kainic acid (KA) into the mouse hippocampus. Focal injection enabled us to separate the effects of proepileptic stimuli initiated by KA injection. Both the injected and contralateral hippocampus participated in the status epilepticus. However, neuronal death induced by KA treatment was restricted to the injected hippocampus, although there was some contralateral axonal degeneration. We profiled gene expression changes in dorsal and ventral regions of both the injected and contralateral hippocampus. Changes were detected in the expression of 1526 transcripts in samples from three time-points: (i) during the KA-induced status epilepticus, (ii) at 2 weeks, before recurrent seizures emerged, and (iii) at 6 months after seizures emerged. Grouping genes with similar spatio-temporal changes revealed an early transcriptional response, strong immune, cell death and growth responses at 2 weeks and an activation of immune and extracellular matrix genes persisting at 6 months. Immunostaining for proteins coded by genes identified from array studies provided evidence for gliogenesis and suggested that the proteoglycan biglycan is synthesized by astrocytes and contributes to a glial scar. Gene changes at 6 months after KA injection were largely restricted to tissue from the injection site. This suggests that either recurrent seizures might depend on maintained processes including immune responses and changes in extracellular matrix proteins near the injection site or alternatively might result from processes, such as growth, distant from the injection site and terminated while seizures are maintained.
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Journal of Neurophysiology, 1990
1. Intracellular recordings were made from neurons in slices of rat nucleus accumbens in vitro. M... more 1. Intracellular recordings were made from neurons in slices of rat nucleus accumbens in vitro. Membrane currents were measured in the potential range -60 to -120 mV with the use of a single-electrode, voltage-clamp amplifier. 2. A minority of neurons (28/285) was identified that had resting membrane potentials almost 20 mV less negative than the majority of the cells. These cells, but not the majority, had an inward current that activated slowly when the cells were hyperpolarized from -60 to -120 mV. The time constant of activation was approximately 3 s at -70 mV and 100 ms at -120 mV. 3. This inward current was completely blocked by external cesium (2 mM) but unaffected by barium. The current was reduced in solutions containing low-sodium concentration and increased in solutions with high-potassium concentration; its reversal potential was estimated to be -36 mV. 4. It is concluded that two types of neuron can be distinguished in the rat nucleus accumbens on the basis of the prese...
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Advances in biochemical psychopharmacology, 1981
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Progress in clinical and biological research, 1983
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Rivista di neurologia
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Rivista di neurologia
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Rivista di neurologia
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Papers by Enrico Cherubini