Altered Expression of Glial Gap Junction Proteins Cx43, Cx30, and Cx47 in the 5XFAD Model of Alzheimer’s Disease
Glial gap junction proteins, called connexins (Cxs), form gap junctions in the central nervous system (CNS) to allow the bidirectional cytosolic exchange of molecules between adjacent cells. Their involvement in inheritable diseases and the use of experimental animal models that closely mimic such d...
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doaj-bd395554dc5742b88542c350134101c62020-11-25T03:55:49ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-10-011410.3389/fnins.2020.582934582934Altered Expression of Glial Gap Junction Proteins Cx43, Cx30, and Cx47 in the 5XFAD Model of Alzheimer’s DiseaseStella Angeli0Stella Angeli1Ioanna Kousiappa2Ioanna Kousiappa3Marios Stavrou4Irene Sargiannidou5Irene Sargiannidou6Elena Georgiou7Elena Georgiou8Savvas S. Papacostas9Savvas S. Papacostas10Savvas S. Papacostas11Savvas S. Papacostas12Kleopas A. Kleopa13Kleopas A. Kleopa14Kleopas A. Kleopa15Kleopas A. Kleopa16Neurobiology Department, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusCyprus School of Molecular Medicine, Nicosia, CyprusNeurobiology Department, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusCyprus School of Molecular Medicine, Nicosia, CyprusDepartment of Electrical and Computer Engineering, Faculty of Engineering, University of Cyprus, Nicosia, CyprusCyprus School of Molecular Medicine, Nicosia, CyprusNeuroscience Department, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusCyprus School of Molecular Medicine, Nicosia, CyprusNeuroscience Department, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusNeurobiology Department, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusCyprus School of Molecular Medicine, Nicosia, CyprusDementia and Cognitive Disorders Center, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusMedical School, University of Nicosia, Nicosia, CyprusCyprus School of Molecular Medicine, Nicosia, CyprusNeuroscience Department, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusCenter for Neuromuscular disorders, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusCenter for Multiple Sclerosis and Related Disorders, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusGlial gap junction proteins, called connexins (Cxs), form gap junctions in the central nervous system (CNS) to allow the bidirectional cytosolic exchange of molecules between adjacent cells. Their involvement in inheritable diseases and the use of experimental animal models that closely mimic such diseases revealed the critical role of glial GJs in myelination and homeostasis. Cxs are also implicated in acquired demyelinating disorders, such as Multiple Sclerosis (MS) and Alzheimer’s disease (AD). Animal and human studies have revealed a role of the astrocytic Cx43 in the progression of AD but the role of Cx47, which is the main partner of Cx43 in the astrocyte-oligodendrocyte GJs is still unknown. The aim of this study was to investigate the astrocytic connexins, Cx43 and Cx30 in relation to oligodendrocytic Cx47 in the cortex and thalamus of the 5XFAD mouse model of AD. The model was characterized by increased Aβ deposition, gliosis, neuronal loss, and memory impairment. Compared to wild-type mice, Cx43 and Cx30 showed increased immunoreactivity in older 5XFAD mice, reflecting astrogliosis, while Cx47 immunoreactivity was reduced. Moreover, Cx47 GJ plaques showed reduced colocalization with Cx43 plaques. Oligodendrocyte precursor cells (OPCs) and mature oligodendrocyte populations were also depleted, and myelin deficits were observed. Our findings indicate reduced astrocyte-oligodendrocyte gap junction connectivity and possibly a shift in Cx43 expression toward astrocyte-astrocyte gap junctions and/or hemichannels, that could impair oligodendrocyte homeostasis and myelination. However, other factors, such as Aβ toxicity, could directly affect oligodendrocyte survival in AD. Our study provides evidence that Cxs might have implications in the progression of AD, although the role of oligodendrocyte Cxs in AD requires further investigation.https://www.frontiersin.org/article/10.3389/fnins.2020.582934/fullAlzheimer’s diseasegap junctionsCx43Cx30Cx47 |
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language |
English |
format |
Article |
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DOAJ |
author |
Stella Angeli Stella Angeli Ioanna Kousiappa Ioanna Kousiappa Marios Stavrou Irene Sargiannidou Irene Sargiannidou Elena Georgiou Elena Georgiou Savvas S. Papacostas Savvas S. Papacostas Savvas S. Papacostas Savvas S. Papacostas Kleopas A. Kleopa Kleopas A. Kleopa Kleopas A. Kleopa Kleopas A. Kleopa |
spellingShingle |
Stella Angeli Stella Angeli Ioanna Kousiappa Ioanna Kousiappa Marios Stavrou Irene Sargiannidou Irene Sargiannidou Elena Georgiou Elena Georgiou Savvas S. Papacostas Savvas S. Papacostas Savvas S. Papacostas Savvas S. Papacostas Kleopas A. Kleopa Kleopas A. Kleopa Kleopas A. Kleopa Kleopas A. Kleopa Altered Expression of Glial Gap Junction Proteins Cx43, Cx30, and Cx47 in the 5XFAD Model of Alzheimer’s Disease Frontiers in Neuroscience Alzheimer’s disease gap junctions Cx43 Cx30 Cx47 |
author_facet |
Stella Angeli Stella Angeli Ioanna Kousiappa Ioanna Kousiappa Marios Stavrou Irene Sargiannidou Irene Sargiannidou Elena Georgiou Elena Georgiou Savvas S. Papacostas Savvas S. Papacostas Savvas S. Papacostas Savvas S. Papacostas Kleopas A. Kleopa Kleopas A. Kleopa Kleopas A. Kleopa Kleopas A. Kleopa |
author_sort |
Stella Angeli |
title |
Altered Expression of Glial Gap Junction Proteins Cx43, Cx30, and Cx47 in the 5XFAD Model of Alzheimer’s Disease |
title_short |
Altered Expression of Glial Gap Junction Proteins Cx43, Cx30, and Cx47 in the 5XFAD Model of Alzheimer’s Disease |
title_full |
Altered Expression of Glial Gap Junction Proteins Cx43, Cx30, and Cx47 in the 5XFAD Model of Alzheimer’s Disease |
title_fullStr |
Altered Expression of Glial Gap Junction Proteins Cx43, Cx30, and Cx47 in the 5XFAD Model of Alzheimer’s Disease |
title_full_unstemmed |
Altered Expression of Glial Gap Junction Proteins Cx43, Cx30, and Cx47 in the 5XFAD Model of Alzheimer’s Disease |
title_sort |
altered expression of glial gap junction proteins cx43, cx30, and cx47 in the 5xfad model of alzheimer’s disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2020-10-01 |
description |
Glial gap junction proteins, called connexins (Cxs), form gap junctions in the central nervous system (CNS) to allow the bidirectional cytosolic exchange of molecules between adjacent cells. Their involvement in inheritable diseases and the use of experimental animal models that closely mimic such diseases revealed the critical role of glial GJs in myelination and homeostasis. Cxs are also implicated in acquired demyelinating disorders, such as Multiple Sclerosis (MS) and Alzheimer’s disease (AD). Animal and human studies have revealed a role of the astrocytic Cx43 in the progression of AD but the role of Cx47, which is the main partner of Cx43 in the astrocyte-oligodendrocyte GJs is still unknown. The aim of this study was to investigate the astrocytic connexins, Cx43 and Cx30 in relation to oligodendrocytic Cx47 in the cortex and thalamus of the 5XFAD mouse model of AD. The model was characterized by increased Aβ deposition, gliosis, neuronal loss, and memory impairment. Compared to wild-type mice, Cx43 and Cx30 showed increased immunoreactivity in older 5XFAD mice, reflecting astrogliosis, while Cx47 immunoreactivity was reduced. Moreover, Cx47 GJ plaques showed reduced colocalization with Cx43 plaques. Oligodendrocyte precursor cells (OPCs) and mature oligodendrocyte populations were also depleted, and myelin deficits were observed. Our findings indicate reduced astrocyte-oligodendrocyte gap junction connectivity and possibly a shift in Cx43 expression toward astrocyte-astrocyte gap junctions and/or hemichannels, that could impair oligodendrocyte homeostasis and myelination. However, other factors, such as Aβ toxicity, could directly affect oligodendrocyte survival in AD. Our study provides evidence that Cxs might have implications in the progression of AD, although the role of oligodendrocyte Cxs in AD requires further investigation. |
topic |
Alzheimer’s disease gap junctions Cx43 Cx30 Cx47 |
url |
https://www.frontiersin.org/article/10.3389/fnins.2020.582934/full |
work_keys_str_mv |
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