P2Y1 receptor inhibition rescues impaired synaptic plasticity and astroglial Ca2+-dependent activity in the epileptic hippocampus

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dc.contributor.authorMartorell A.
dc.contributor.authorWellmann M.
dc.contributor.authorGuiffa F.
dc.contributor.authorFuenzalida M.
dc.contributor.authorBonansco C.
dc.date.accessioned2021-09-08T22:20:15Z
dc.date.available2021-09-08T22:20:15Z
dc.date.issued2020-12
dc.descriptionIndexación Scopuses
dc.description.abstractEpilepsy is characterized by a progressive predisposition to suffer seizures due to neuronal hyperexcitability, and one of its most common co-morbidities is cognitive decline. In animal models of chronic epilepsy, such as kindling, electrically induced seizures impair long-term potentiation (LTP), deteriorating learning and memory performance. Astrocytes are known to actively modulate synaptic plasticity and neuronal excitability through Ca2+-dependent gliotransmitter release. It is unclear, however, if astroglial Ca2+ signaling could contribute to the development of synaptic plasticity alterations in the epileptic hippocampus. By employing electrophysiological tools and Ca2+ imaging, we found that glutamatergic CA3-CA1 synapses from kindled rats exhibit an impairment in theta burst (TBS) and high frequency stimulation (HFS)-induced LTP, which is accompanied by an increased probability of neurotransmitter release (Pr) and an abnormal pattern of astroglial Ca2+-dependent transients. Both the impairment in LTP and the Pr were reversed by inhibiting purinergic P2Y1 receptors (P2Y1R) with the specific antagonist MRS2179, which also restored the spontaneous and TBS-induced pattern of astroglial Ca2+-dependent signals. Two consecutive, spaced TBS protocols also failed to induce LTP in the kindled group, however, this impairment was reversed and a strong LTP was induced when the second TBS was applied in the presence of MRS2179, suggesting that the mechanisms underlying the alterations in TBS-induced LTP are likely associated with an aberrant modulation of the induction threshold for LTP. Altogether, these results indicate that P2Y1R inhibition rescues both the pattern of astroglial Ca2+-activity and the plastic properties of CA3-CA1 synapses in the epileptic hippocampus, suggesting that astrocytes might take part in the mechanisms that deteriorate synaptic plasticity and thus cause cognitive decline in epileptic patients. © 2020es
dc.description.urihttps://www-sciencedirect-com.recursosbiblioteca.unab.cl/science/article/pii/S0969996120304071?via%3Dihub
dc.identifier.citationNeurobiology of Disease, Volume 146December 2020 Article number 105132es
dc.identifier.doi10.1016/j.nbd.2020.105132
dc.identifier.issn09699961
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/20218
dc.language.isoenes
dc.publisherAcademic Press Inc.es
dc.subjectAstrocyteses
dc.subjectNeurogliaes
dc.subjectCalcium Signalinges
dc.titleP2Y1 receptor inhibition rescues impaired synaptic plasticity and astroglial Ca2+-dependent activity in the epileptic hippocampuses
dc.typeArtículoes
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