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Involvement of DAAO Overexpression in Delayed Hippocampal Neuronal Death.
Liu, Hao; Zhang, Jun-Tao; Mou, Chen-Ye; Hao, Yue; Cui, Wei.
Afiliação
  • Liu H; Department of Ophthalmology, The Affiliated People's Hospital of Ningbo University, Ningbo 315040, China.
  • Zhang JT; School of Medicine, Ningbo University, Ningbo 315211, China.
  • Mou CY; Department of Ophthalmology, The Affiliated People's Hospital of Ningbo University, Ningbo 315040, China.
  • Hao Y; School of Medicine, Ningbo University, Ningbo 315211, China.
  • Cui W; Department of Ophthalmology, The Affiliated People's Hospital of Ningbo University, Ningbo 315040, China.
Cells ; 11(22)2022 11 21.
Article em En | MEDLINE | ID: mdl-36429117
BACKGROUND: D-amino acid oxidase (DAAO) is a flavoenzyme that specifically catalyzes the deamination of many neutral and basic D-amino acids. This study aims to explore the pathological increment of hippocampal DAAO and its potential relationship with delayed hippocampal neuronal death. METHODS: Ischemia-reperfusion was induced in mice through middle cerebral artery occlusion (MCAO). Neurological deficit scores and hippocampal neuronal death were assessed in MCAO mice. Immunofluorescent staining was applied to identify activated astrocytes and evaluate DAAO expression. TUNEL and Nissl staining were utilized to identify cell apoptosis of hippocampal neurons. RESULTS: Hippocampal astrocytic DAAO was strikingly increased following ischemic stroke, with the greatest increase on day 5 after surgery, followed by the manifestation of neurobehavioral deficits. Astrocytic DAAO was found to be mainly expressed in the hippocampal CA2 region and linked with subsequent specific neural apoptosis. Thus, it is supposed that the activation of astrocytic DAAO in ischemic stroke might contribute to neuronal death. An intravenous, twice-daily administration of 4H-furo[3,2-b]pyrrole-5-carboxylic acid (SUN, 10 mg/kg) markedly relieved behavioral status and delayed hippocampal neuronal death by 38.0% and 41.5%, respectively, compared to the model group treated with saline. In transfected primary astrocytes, DAAO overexpression inhibits cell activity, induces cytotoxicity, and promotes hippocampal neuronal death at least partly by enhancing H2O2 levels with subsequent activation of TRP calcium channels in neurons. CONCLUSIONS: Our findings suggest that increased hippocampal DAAO is causally associated with the development of delayed neuronal death after MCAO onset via astrocyte-neuron interactions. Hence, targeting DAAO is a promising therapeutic strategy for the management of neurological disorders.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: AVC Isquêmico / Peróxido de Hidrogênio Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: AVC Isquêmico / Peróxido de Hidrogênio Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article