Orientador: Prof. Dr. Alexandre Hiroaki Kihara / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Neurociência e Cognição, 2016. / Status epilepticus (SE) is a clinical emergency that can lead to the development
of temporal lobe epilepsy (TLE). The term epileptogenesis refers to the transformation
of physiological neuronal networks into a dysfunctional state. In most patients
presenting TLE, the development and maintenance of spontaneous seizures are linked
with calcium (Ca+2)-dependent processes like neuronal loss, reactive gliosis and
pathological neuronal plasticity. It has been shown that SE produces an increase in
ryanodine receptor-dependent intracellular Ca+2 levels in hippocampal neurons, which
remain elevated during the progression of the disease. In this context, the aim of this
work was to investigate the effects of ryanodine receptors (RyRs) inhibition on the
expression of important synaptic and plasticity-related proteins during the latent period
of the pilocarpine model of TLE. First, we performed western blot and immunolabeling
analyses in order to evaluate the pattern of distribution of the activity-regulated
cytoskeleton-associated protein (ARC) in the rat hippocampus during the latent period.
We observed decrease of the total protein levels 48 hours after SE, together with downregulation of its nuclear immunolabeling in granular cells of the dentate gyrus (DG). In
addition, we observed the appearance of intense ARC immunoreactive neurons
(IAINs) colocalizing mainly with excitatory neurons in CA1, CA3 and hilus.
Intrahippocampal injections of the RyRs blocker dantrolene increased the total protein
levels of the presynaptic protein synapsin I (SYN I) 48 hours after SE. We also
observed up-regulation of SYN I and synaptophysin (SYP) in hippocampal regions
known to receive important synaptic inputs. Finally, dantrolene showed
neuroprotective effects by decreasing neuronal loss in CA1 and CA3 of experimental
hippocampi. Our results suggest that ARC might be participating in the overall
hippocampal reorganization and increase of excitability observed during
epileptogenesis. In addition, RyRs may contribute to trigger the hippocampal
neurodegeneration and synaptic alterations that lead to the development of acquired
epilepsy.
| Identifer | oai:union.ndltd.org:IBICT/oai:BDTD:79334 |
| Date | January 2016 |
| Creators | Rodriguez, Pedro Xavier Royero |
| Contributors | Kihara, Alexandre Hiroaki, Echeverry, Marcela Bermúdez, Valle, Angela Cristina do |
| Source Sets | IBICT Brazilian ETDs |
| Language | Inglês |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf, 87 f. : il. |
| Source | reponame:Repositório Institucional da UFABC, instname:Universidade Federal do ABC, instacron:UFABC |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | http://biblioteca.ufabc.edu.br/index.php?codigo_sophia=79334&midiaext=71901, http://biblioteca.ufabc.edu.br/index.php?codigo_sophia=79334&midiaext=71902, Cover: http://biblioteca.ufabc.edu.brphp/capa.php?obra=79334 |
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