Year: 2022
Type: article
Abstract: Background: D-Amino acid oxidase (DAAO) is a flavoenzyme specifically catalyzing oxidative deamination of neutral and basic D-amino acids. This study aimed to explore the association between increased hippocampal DAAO and the development of delayed hippocampal neuronal death. Ischemic stroke was induced in mice by middle cerebral artery occlusion (MCAO). Methods: Neurological deficit score 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 in ischemic stroke, with peak increase on Day 5 after surgery, followed with successive neurobehavioral deficits. Astrocytic DAAO was mainly expressed in hippocampal CA2, followed with specific neural apoptosis. Thus it was supposed that activation of astrocytic DAAO in ischemic stroke might contribute to neuronal death. The intravenous multiple 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, overexpression of DAAO inhibited cell activity, exhibited cytotoxicity, and finally promoted hippocampal neuronal death. TRP calcium channel and H2O2 might be involved in DAAO-induced neuronal apoptosis. Conclusion: Our findings suggest that increased hippocampal DAAO was causally associated with the development of delayed neuronal death after MCAO onset, and that targeting DAAO would be a latent modality for the management of neurological disorders. Funding Information: This study was supported in part by grants from National Natural Science Foundation of China (82101392), Zhejiang Provincial Natural Science Foundation (LQ21H090002) and Ningbo Science and Technology Program (202003N4117). Many thanks for tremendous favors from all members in kingslab of Shanghai Jiao Tong University and professor Cui’s team group in Ningbo University. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Not applicable for humans since there are no human subjects or samples in this study. The animal protocols were approved by the Animal Care and Welfare Committee of Shanghai Jiao Tong University (Shanghai, China) and conducted in compliance with the Guide for Care and Use of Laboratory Animals, and the Animals in Research: Reporting In Vivo Experiments (ARRIVE) guidelines.
Source: Cells
Authors: Hao Liu, Jun-Tao Zhang, Chen-Ye Mou, Yue Hao, Wei Cui
Institution: Ningbo University
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,303
OpenAlex ID: W4309740733