Glia can influence the outcome of an epileptogenic insult by controlling the recovery of neuronalnetworks and functions. In particular, glia may facilitate the establishment of epilepsy by impairedremoval of glutamate from synapses or by releasing inflammatory cytokines and excitatoryneurotransmitters, such as interleukin-1β or, respectively, glutamate, aspartate and D-serine.Opposed to these pro-excitatory/pro-epileptogenic mediators, glia can also release molecules thatrestrain neuronal excitability such as neurosteroids, which are potent modulators of inhibitorycurrents dependent on γ-aminobutyric acid (GABA) type A receptors. In normal conditions,neurosteroids are mainly synthesized in neurons by conversion of cholesterol to pregnenolone, a stepcatalyzed by the cytochrome P450 cholesterol-side chain cleavage enzyme (P450scc). Following anepileptogenic insult, astrocytes transform into reactive cells and express high levels of P450scc, thusbecoming major players in neurosteroid synthesis. In this context, we found that the degree ofP450scc expression in astrocytes dictates the duration of the latent period. In line with this view,inhibition of neurosteroid synthesis anticipates the establishment of chronic epilepsy only when theP450scc induction is intense and long lasting. Thus, we hypothesize that reactive astrocytes maydampen neuronal excitability in the course of epileptogenesis through neurosteroid-mediatedmechanisms that likely enhance GABAergic neurotransmission.
Glia-neuron interactions: neurosteroids and epileptogenesis / Biagini, Giuseppe; C., Marinelli; G., Panuccio; Puja, Giulia; M., Avoli. - STAMPA. - 80(2012), pp. 635-647.
Data di pubblicazione: | 2012 |
Titolo: | Glia-neuron interactions: neurosteroids and epileptogenesis. |
Autore/i: | Biagini, Giuseppe; C., Marinelli; G., Panuccio; Puja, Giulia; M., Avoli |
Autore/i UNIMORE: | |
Titolo del libro: | Jasper's Basic Mechanisms of the Epilepsies Fourth Edition |
Editore: | Oxford University Press |
Nazione editore: | STATI UNITI D'AMERICA |
Citazione: | Glia-neuron interactions: neurosteroids and epileptogenesis / Biagini, Giuseppe; C., Marinelli; G., Panuccio; Puja, Giulia; M., Avoli. - STAMPA. - 80(2012), pp. 635-647. |
Tipologia | Capitolo/Saggio |
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