Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation
Connexin 30 (Cx30), which forms gap junctions between astrocytes, regulates cell adhesion and migration, and modulates glutamate transport. Cx30 is upregulated on activated astroglia in central nervous system inflammatory lesions, including spinal cord lesions in mutant superoxide dismutase 1 (mSOD1...
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2022-12-01
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/16046 |
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| author | Yu Hashimoto Ryo Yamasaki Senri Ko Eriko Matsuo Yuko Kobayakawa Katsuhisa Masaki Dai Matsuse Noriko Isobe |
| author_facet | Yu Hashimoto Ryo Yamasaki Senri Ko Eriko Matsuo Yuko Kobayakawa Katsuhisa Masaki Dai Matsuse Noriko Isobe |
| author_sort | Yu Hashimoto |
| collection | DOAJ |
| description | Connexin 30 (Cx30), which forms gap junctions between astrocytes, regulates cell adhesion and migration, and modulates glutamate transport. Cx30 is upregulated on activated astroglia in central nervous system inflammatory lesions, including spinal cord lesions in mutant superoxide dismutase 1 (mSOD1) transgenic amyotrophic lateral sclerosis (ALS) model mice. Here, we investigated the role of Cx30 in mSOD1 mice. Cx30 was highly expressed in the pre-onset stage in mSOD1 mice. mSOD1 mice with knockout (KO) of the <i>Cx30</i> gene (<i>Cx30</i>KO-mSOD1 mice) showed delayed disease onset and tended to have an extended survival period (log-rank, <i>p</i> = 0.09). At the progressive and end stages of the disease, anterior horn cells were significantly preserved in <i>Cx30</i>KO-mSOD1 mice. In lesions of these mice, glial fibrillary acidic protein/C3-positive inflammatory astroglia were decreased. Additionally, the activation of astrocytes in <i>Cx30</i>KO-mSOD1 mice was reduced compared with mSOD1 mice by gene expression microarray. Furthermore, expression of connexin 43 at the pre-onset stage was downregulated in <i>Cx30</i>KO-mSOD1 mice. These findings suggest that reduced expression of astroglial Cx30 at the early disease stage in ALS model mice protects neurons by attenuating astroglial inflammation. |
| first_indexed | 2024-03-09T16:18:58Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:18:58Z |
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| spelling | doaj.art-9c46d7f79a01481d9c283de359581a392023-11-24T15:31:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241604610.3390/ijms232416046Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial InflammationYu Hashimoto0Ryo Yamasaki1Senri Ko2Eriko Matsuo3Yuko Kobayakawa4Katsuhisa Masaki5Dai Matsuse6Noriko Isobe7Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanConnexin 30 (Cx30), which forms gap junctions between astrocytes, regulates cell adhesion and migration, and modulates glutamate transport. Cx30 is upregulated on activated astroglia in central nervous system inflammatory lesions, including spinal cord lesions in mutant superoxide dismutase 1 (mSOD1) transgenic amyotrophic lateral sclerosis (ALS) model mice. Here, we investigated the role of Cx30 in mSOD1 mice. Cx30 was highly expressed in the pre-onset stage in mSOD1 mice. mSOD1 mice with knockout (KO) of the <i>Cx30</i> gene (<i>Cx30</i>KO-mSOD1 mice) showed delayed disease onset and tended to have an extended survival period (log-rank, <i>p</i> = 0.09). At the progressive and end stages of the disease, anterior horn cells were significantly preserved in <i>Cx30</i>KO-mSOD1 mice. In lesions of these mice, glial fibrillary acidic protein/C3-positive inflammatory astroglia were decreased. Additionally, the activation of astrocytes in <i>Cx30</i>KO-mSOD1 mice was reduced compared with mSOD1 mice by gene expression microarray. Furthermore, expression of connexin 43 at the pre-onset stage was downregulated in <i>Cx30</i>KO-mSOD1 mice. These findings suggest that reduced expression of astroglial Cx30 at the early disease stage in ALS model mice protects neurons by attenuating astroglial inflammation.https://www.mdpi.com/1422-0067/23/24/16046amyotrophic lateral sclerosisALSSOD1mSOD1 miceconnexin 30astrocytes |
| spellingShingle | Yu Hashimoto Ryo Yamasaki Senri Ko Eriko Matsuo Yuko Kobayakawa Katsuhisa Masaki Dai Matsuse Noriko Isobe Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation International Journal of Molecular Sciences amyotrophic lateral sclerosis ALS SOD1 mSOD1 mice connexin 30 astrocytes |
| title | Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation |
| title_full | Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation |
| title_fullStr | Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation |
| title_full_unstemmed | Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation |
| title_short | Connexin 30 Deficiency Ameliorates Disease Progression at the Early Phase in a Mouse Model of Amyotrophic Lateral Sclerosis by Suppressing Glial Inflammation |
| title_sort | connexin 30 deficiency ameliorates disease progression at the early phase in a mouse model of amyotrophic lateral sclerosis by suppressing glial inflammation |
| topic | amyotrophic lateral sclerosis ALS SOD1 mSOD1 mice connexin 30 astrocytes |
| url | https://www.mdpi.com/1422-0067/23/24/16046 |
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