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AQP4 knockout promotes neurite outgrowth via upregulating GAP43 expression in infant rats with hypoxic‐ischemic brain injury

Neonatal hypoxic‐ischemic encephalopathy (NHIE) induces severe cerebral damage and neurological dysfunction, with seldom effective therapy. Aquaporin‐4 (AQP4) is involved in aggravating brain damage induced by NHIE. This study aimed to investigate the role of AQP4 underlying the pathogenesis of NHIE...

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Autores principales: Dan, Qi‐Qin, Ma, Zheng, Tan, Ya‐Xin, Visar, Belegu, Chen, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528973/
https://www.ncbi.nlm.nih.gov/pubmed/37786741
http://dx.doi.org/10.1002/ibra.12062
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author Dan, Qi‐Qin
Ma, Zheng
Tan, Ya‐Xin
Visar, Belegu
Chen, Li
author_facet Dan, Qi‐Qin
Ma, Zheng
Tan, Ya‐Xin
Visar, Belegu
Chen, Li
author_sort Dan, Qi‐Qin
collection PubMed
description Neonatal hypoxic‐ischemic encephalopathy (NHIE) induces severe cerebral damage and neurological dysfunction, with seldom effective therapy. Aquaporin‐4 (AQP4) is involved in aggravating brain damage induced by NHIE. This study aimed to investigate the role of AQP4 underlying the pathogenesis of NHIE. Neonatal Sprague–Dawley rats were used to establish neonatal hypoxic‐ischemic (HI) models, and the expression of AQP4 in the cortex, hippocampus, and lung tissues was detected by real‐time quantitative polymerase chain reaction as well as Western blot. Primary cortical neurons were cultured for the oxygen‐glucose deprivation (OGD) model, and siRNA was used to silence the expression of AQP4. Immunostaining of Tuj1 was performed to observe the axonal growth. CRISPER/Cas9 technology was used to knock out AQP4. The results demonstrated that AQP4 was upregulated in the cortex, hippocampus, and lung tissues in neonatal rats with HI and OGD neurons. Besides, silencing AQP4 promoted axonal growth of OGD neurons, and AQP4 knockout notably improved long‐term neurobehavioral impairment. Furthermore, GAP43 was found closely correlated with AQP4 via GeneMANIA prediction. Significant downregulation of GAP43 was induced in OGD neurons, while AQP4 knockout markedly upregulated its expression in rats. This indicated that the depletion of AQP4 may enhance axonal regeneration and promote the long‐term neurobehavioral recovery associated with the upregulation of GAP43 expression.
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spelling pubmed-105289732023-10-02 AQP4 knockout promotes neurite outgrowth via upregulating GAP43 expression in infant rats with hypoxic‐ischemic brain injury Dan, Qi‐Qin Ma, Zheng Tan, Ya‐Xin Visar, Belegu Chen, Li Ibrain Original Articles Neonatal hypoxic‐ischemic encephalopathy (NHIE) induces severe cerebral damage and neurological dysfunction, with seldom effective therapy. Aquaporin‐4 (AQP4) is involved in aggravating brain damage induced by NHIE. This study aimed to investigate the role of AQP4 underlying the pathogenesis of NHIE. Neonatal Sprague–Dawley rats were used to establish neonatal hypoxic‐ischemic (HI) models, and the expression of AQP4 in the cortex, hippocampus, and lung tissues was detected by real‐time quantitative polymerase chain reaction as well as Western blot. Primary cortical neurons were cultured for the oxygen‐glucose deprivation (OGD) model, and siRNA was used to silence the expression of AQP4. Immunostaining of Tuj1 was performed to observe the axonal growth. CRISPER/Cas9 technology was used to knock out AQP4. The results demonstrated that AQP4 was upregulated in the cortex, hippocampus, and lung tissues in neonatal rats with HI and OGD neurons. Besides, silencing AQP4 promoted axonal growth of OGD neurons, and AQP4 knockout notably improved long‐term neurobehavioral impairment. Furthermore, GAP43 was found closely correlated with AQP4 via GeneMANIA prediction. Significant downregulation of GAP43 was induced in OGD neurons, while AQP4 knockout markedly upregulated its expression in rats. This indicated that the depletion of AQP4 may enhance axonal regeneration and promote the long‐term neurobehavioral recovery associated with the upregulation of GAP43 expression. John Wiley and Sons Inc. 2022-08-19 /pmc/articles/PMC10528973/ /pubmed/37786741 http://dx.doi.org/10.1002/ibra.12062 Text en © 2022 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University (AHZMU) and Wiley‐VCH GmbH. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Dan, Qi‐Qin
Ma, Zheng
Tan, Ya‐Xin
Visar, Belegu
Chen, Li
AQP4 knockout promotes neurite outgrowth via upregulating GAP43 expression in infant rats with hypoxic‐ischemic brain injury
title AQP4 knockout promotes neurite outgrowth via upregulating GAP43 expression in infant rats with hypoxic‐ischemic brain injury
title_full AQP4 knockout promotes neurite outgrowth via upregulating GAP43 expression in infant rats with hypoxic‐ischemic brain injury
title_fullStr AQP4 knockout promotes neurite outgrowth via upregulating GAP43 expression in infant rats with hypoxic‐ischemic brain injury
title_full_unstemmed AQP4 knockout promotes neurite outgrowth via upregulating GAP43 expression in infant rats with hypoxic‐ischemic brain injury
title_short AQP4 knockout promotes neurite outgrowth via upregulating GAP43 expression in infant rats with hypoxic‐ischemic brain injury
title_sort aqp4 knockout promotes neurite outgrowth via upregulating gap43 expression in infant rats with hypoxic‐ischemic brain injury
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528973/
https://www.ncbi.nlm.nih.gov/pubmed/37786741
http://dx.doi.org/10.1002/ibra.12062
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