title: Functional Role of Intracellular Calcium Receptor Inositol 1,4,5-Trisphosphate Type 1 in Rat Hippocampus after Neonatal Anoxia.
abstract: Anoxia is one of the most prevalent causes of neonatal morbidity and mortality, especially in preterm neonates, constituting an important public health problem due to permanent neurological sequelae observed in patients. Oxygen deprivation triggers a series of simultaneous cascades, culminating in cell death mainly located in more vulnerable metabolic brain regions, such as the hippocampus. In the process of cell death by oxygen deprivation, cytosolic calcium plays crucial roles. Intracellular inositol 1,4,5-trisphosphate receptors (IP3Rs) are important regulators of cytosolic calcium levels, although the role of these receptors in neonatal anoxia is completely unknown. This study focused on the functional role of inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) in rat hippocampus after neonatal anoxia. Quantitative real-time PCR revealed a decrease of IP3R1 gene expression 24 hours after neonatal anoxia. We detected that IP3R1 accumulates specially in CA1, and this spatial pattern did not change after neonatal anoxia. Interestingly, we observed that anoxia triggers translocation of IP3R1 to nucleus in hippocampal cells. We were able to observe that anoxia changes distribution of IP3R1 immunofluorescence signals, as revealed by cluster size analysis. We next examined the role of IP3R1 in the neuronal cell loss triggered by neonatal anoxia. Intrahippocampal injection of non-specific IP3R1 blocker 2-APB clearly reduced the number of Fluoro-Jade C and Tunel positive cells, revealing that activation of IP3R1 increases cell death after neonatal anoxia. Finally, we aimed to disclose mechanistics of IP3R1 in cell death. We were able to determine that blockade of IP3R1 did not reduced the distribution and pixel density of activated caspase 3-positive cells, indicating that the participation of IP3R1 in neuronal cell loss is not related to classical caspase-mediated apoptosis. In summary, this study may contribute to new perspectives in the investigation of neurodegenerative mechanisms triggered by oxygen deprivation.
authors.affiliation: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, São Paulo, Brazil.
authors.forename: Juliane Midori
authors.initials: JM
authors.lastname: Ikebara
authors.affiliation: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, São Paulo, Brazil.
authors.forename: Silvia Honda
authors.initials: SH
authors.lastname: Takada
authors.affiliation: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, São Paulo, Brazil.
authors.forename: Débora Sterzeck
authors.initials: DS
authors.lastname: Cardoso
authors.affiliation: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, São Paulo, Brazil.
authors.forename: Natália Myuki Moralles
authors.initials: NM
authors.lastname: Dias
authors.affiliation: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, São Paulo, Brazil.
authors.forename: Beatriz Crossiol Vicente
authors.initials: BC
authors.lastname: de Campos
authors.affiliation: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, São Paulo, Brazil.
authors.forename: Talitha Amanda Sanches
authors.initials: TA
authors.lastname: Bretherick
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Guilherme Shigueto Vilar
authors.initials: GS
authors.lastname: Higa
authors.affiliation: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, São Paulo, Brazil.
authors.forename: Mariana Sacrini Ayres
authors.initials: MS
authors.lastname: Ferraz
authors.affiliation: Laboratório de Neurogenética, Universidade Federal do ABC, São Bernardo do Campo, São Paulo, Brazil.|Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Alexandre Hiroaki
authors.identifier: http://orcid.org/0000-0002-4027-7261
authors.initials: AH
authors.lastname: Kihara
mesh_terms: D000818:Animals; D017209:Apoptosis; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D020013:Calcium Signaling; D000860:Hypoxia / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; C488910:Itpr1 protein, rat