Enhanced Astrocyte Activity and Excitatory Synaptic Function in the Hippocampus of Pentylenetetrazole Kindling Model of Epilepsy

dc.contributor.authorDíaz, Franco
dc.contributor.authorAguilar, Freddy
dc.contributor.authorWellmann, Mario
dc.contributor.authorMartorell, Andrés
dc.contributor.authorGonzález-Arancibia, Camila
dc.contributor.authorChacana-Véliz, Lorena
dc.contributor.authorNegrón-Oyarzo, Ignacio
dc.contributor.authorChávez, Andrés E.
dc.contributor.authorFuenzalida, Marco
dc.contributor.authorNualart, Francisco
dc.contributor.authorSotomayor-Zárate, Ramón
dc.contributor.authorBonansco, Christian
dc.date.accessioned2024-02-19T17:46:05Z
dc.date.available2024-02-19T17:46:05Z
dc.date.issued2023-09-25
dc.description.abstractEpilepsy is a chronic condition characterized by recurrent spontaneous seizures. The interaction between astrocytes and neurons has been suggested to play a role in the abnormal neuronal activity observed in epilepsy. However, the exact way astrocytes influence neuronal activity in the epileptogenic brain remains unclear. Here, using the PTZ-induced kindling mouse model, we evaluated the interaction between astrocyte and synaptic function by measuring astrocytic Ca2+ activity, neuronal excitability, and the excitatory/inhibitory balance in the hippocampus. Compared to control mice, hippocampal slices from PTZ-kindled mice displayed an increase in glial fibrillary acidic protein (GFAP) levels and an abnormal pattern of intracellular Ca2+-oscillations, characterized by an increased frequency of prolonged spontaneous transients. PTZ-kindled hippocampal slices also showed an increase in the E/I ratio towards excitation, likely resulting from an augmented release probability of excitatory inputs without affecting inhibitory synapses. Notably, the alterations in the release probability seen in PTZ-kindled slices can be recovered by reducing astrocyte hyperactivity with the reversible toxin fluorocitrate. This suggests that astroglial hyper-reactivity enhances excitatory synaptic transmission, thereby impacting the E/I balance in the hippocampus. Altogether, our findings support the notion that abnormal astrocyte–neuron interactions are pivotal mechanisms in epileptogenesis.
dc.identifier.issn10.3390/ijms241914506
dc.identifier.other1422-0067
dc.identifier.urihttps://hdl.handle.net/20.500.12536/2117
dc.language.isoen
dc.sourceInternational Journal of Molecular Sciences
dc.subjectAstrogliosis
dc.subjectGliotransmission
dc.subjectExcitation–inhibition imbalance
dc.subjectRelease probability
dc.subjectPTZ-induced kindling
dc.subjectEpilepsy
dc.titleEnhanced Astrocyte Activity and Excitatory Synaptic Function in the Hippocampus of Pentylenetetrazole Kindling Model of Epilepsy
dc.typeArticle
uvm.carreraFonoaudiología
uvm.escuelaEscuela de Ciencias de la salud
uvm.indexWoS
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