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FAM3A Ameliorates Brain Impairment Induced by Hypoxia–Ischemia in Neonatal Rat
ABSTRACT: Hypoxia–ischemia (HI) during crucial periods of brain formation can lead to changes in brain morphology, propagation of neuronal stimuli, and permanent neurodevelopmental impairment, which can have profound effects on cognitive function later in life. FAM3A, a subgroup of family with seque...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9813043/ https://www.ncbi.nlm.nih.gov/pubmed/34853925 http://dx.doi.org/10.1007/s10571-021-01172-6 |
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author | Song, Qing Gao, Qingying Chen, Taotao Wen, Ting Wu, Peng Luo, Xiao Chen, Qiao Yi |
author_facet | Song, Qing Gao, Qingying Chen, Taotao Wen, Ting Wu, Peng Luo, Xiao Chen, Qiao Yi |
author_sort | Song, Qing |
collection | PubMed |
description | ABSTRACT: Hypoxia–ischemia (HI) during crucial periods of brain formation can lead to changes in brain morphology, propagation of neuronal stimuli, and permanent neurodevelopmental impairment, which can have profound effects on cognitive function later in life. FAM3A, a subgroup of family with sequence similarity 3 (FAM3) gene family, is ubiquitously expressed in almost all cells. Overexpression of FAM3A has been evidenced to reduce hyperglycemia via the PI3K/Akt signaling pathway and protect mitochondrial function in neuronal HT22 cells. This study aims to evaluate the protective role of FAM3A in HI-induced brain impairment. Experimentally, maternal rats underwent uterine artery bilateral ligation to induce neonatal HI on day 14 of gestation. At 6 weeks of age, cognitive development assessments including NSS, wire grip, and water maze were carried out. The animals were then sacrificed to assess cerebral mitochondrial function as well as levels of FAM3A, TNF-α and IFN-γ. Results suggest that HI significantly reduced FAM3A expression in rat brain tissues, and that overexpression of FAM3A through lentiviral transduction effectively improved cognitive and motor functions in HI rats as reflected by improved NSS evaluation, cerebral water content, limb strength, as well as spatial learning and memory. At the molecular level, overexpression of FAM3A was able to promote ATP production, balance mitochondrial membrane potential, and reduce levels of pro-inflammatory cytokines TNF-α and IFN-γ. We conclude that FAM3A overexpression may have a protective effect on neuron morphology, cerebral mitochondrial as well as cognitive function. GRAPHICAL ABSTRACT: [Figure: see text] |
format | Online Article Text |
id | pubmed-9813043 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-98130432023-01-06 FAM3A Ameliorates Brain Impairment Induced by Hypoxia–Ischemia in Neonatal Rat Song, Qing Gao, Qingying Chen, Taotao Wen, Ting Wu, Peng Luo, Xiao Chen, Qiao Yi Cell Mol Neurobiol Original Research ABSTRACT: Hypoxia–ischemia (HI) during crucial periods of brain formation can lead to changes in brain morphology, propagation of neuronal stimuli, and permanent neurodevelopmental impairment, which can have profound effects on cognitive function later in life. FAM3A, a subgroup of family with sequence similarity 3 (FAM3) gene family, is ubiquitously expressed in almost all cells. Overexpression of FAM3A has been evidenced to reduce hyperglycemia via the PI3K/Akt signaling pathway and protect mitochondrial function in neuronal HT22 cells. This study aims to evaluate the protective role of FAM3A in HI-induced brain impairment. Experimentally, maternal rats underwent uterine artery bilateral ligation to induce neonatal HI on day 14 of gestation. At 6 weeks of age, cognitive development assessments including NSS, wire grip, and water maze were carried out. The animals were then sacrificed to assess cerebral mitochondrial function as well as levels of FAM3A, TNF-α and IFN-γ. Results suggest that HI significantly reduced FAM3A expression in rat brain tissues, and that overexpression of FAM3A through lentiviral transduction effectively improved cognitive and motor functions in HI rats as reflected by improved NSS evaluation, cerebral water content, limb strength, as well as spatial learning and memory. At the molecular level, overexpression of FAM3A was able to promote ATP production, balance mitochondrial membrane potential, and reduce levels of pro-inflammatory cytokines TNF-α and IFN-γ. We conclude that FAM3A overexpression may have a protective effect on neuron morphology, cerebral mitochondrial as well as cognitive function. GRAPHICAL ABSTRACT: [Figure: see text] Springer US 2021-12-01 2023 /pmc/articles/PMC9813043/ /pubmed/34853925 http://dx.doi.org/10.1007/s10571-021-01172-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Research Song, Qing Gao, Qingying Chen, Taotao Wen, Ting Wu, Peng Luo, Xiao Chen, Qiao Yi FAM3A Ameliorates Brain Impairment Induced by Hypoxia–Ischemia in Neonatal Rat |
title | FAM3A Ameliorates Brain Impairment Induced by Hypoxia–Ischemia in Neonatal Rat |
title_full | FAM3A Ameliorates Brain Impairment Induced by Hypoxia–Ischemia in Neonatal Rat |
title_fullStr | FAM3A Ameliorates Brain Impairment Induced by Hypoxia–Ischemia in Neonatal Rat |
title_full_unstemmed | FAM3A Ameliorates Brain Impairment Induced by Hypoxia–Ischemia in Neonatal Rat |
title_short | FAM3A Ameliorates Brain Impairment Induced by Hypoxia–Ischemia in Neonatal Rat |
title_sort | fam3a ameliorates brain impairment induced by hypoxia–ischemia in neonatal rat |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9813043/ https://www.ncbi.nlm.nih.gov/pubmed/34853925 http://dx.doi.org/10.1007/s10571-021-01172-6 |
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