Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation

This study evaluated whether GM(2) ganglioside storage is necessary for neurodegeneration and neuroinflammation by performing β-hexosaminidase rescue experiments in neurons of HexB(−/−) mice. We developed a novel mouse model, whereby the expression of the human HEXB gene was targeted to neurons of H...

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Autores principales: Kyrkanides, Stephanos, Brouxhon, Sabine M, Tallents, Ross H, Miller, Jen-nie H, Olschowka, John A, O’Banion, M Kerry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458890/
https://www.ncbi.nlm.nih.gov/pubmed/22863301
http://dx.doi.org/10.1186/1742-2094-9-186
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author Kyrkanides, Stephanos
Brouxhon, Sabine M
Tallents, Ross H
Miller, Jen-nie H
Olschowka, John A
O’Banion, M Kerry
author_facet Kyrkanides, Stephanos
Brouxhon, Sabine M
Tallents, Ross H
Miller, Jen-nie H
Olschowka, John A
O’Banion, M Kerry
author_sort Kyrkanides, Stephanos
collection PubMed
description This study evaluated whether GM(2) ganglioside storage is necessary for neurodegeneration and neuroinflammation by performing β-hexosaminidase rescue experiments in neurons of HexB(−/−) mice. We developed a novel mouse model, whereby the expression of the human HEXB gene was targeted to neurons of HexB(−/−) mice by the Thy1 promoter. Despite β-hexosaminidase restoration in neurons was sufficient in rescuing HexB(−/−) mice from GM(2) neuronal storage and neurodegeneration, brain inflammation persisted, including the presence of large numbers of reactive microglia/macrophages due to persisting GM(2) presence in this cell type. In conclusion, our results suggest that neuroinflammation is not sufficient to elicit neurodegeneration as long as neuronal function is restored.
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spelling pubmed-34588902012-09-27 Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation Kyrkanides, Stephanos Brouxhon, Sabine M Tallents, Ross H Miller, Jen-nie H Olschowka, John A O’Banion, M Kerry J Neuroinflammation Research This study evaluated whether GM(2) ganglioside storage is necessary for neurodegeneration and neuroinflammation by performing β-hexosaminidase rescue experiments in neurons of HexB(−/−) mice. We developed a novel mouse model, whereby the expression of the human HEXB gene was targeted to neurons of HexB(−/−) mice by the Thy1 promoter. Despite β-hexosaminidase restoration in neurons was sufficient in rescuing HexB(−/−) mice from GM(2) neuronal storage and neurodegeneration, brain inflammation persisted, including the presence of large numbers of reactive microglia/macrophages due to persisting GM(2) presence in this cell type. In conclusion, our results suggest that neuroinflammation is not sufficient to elicit neurodegeneration as long as neuronal function is restored. BioMed Central 2012-08-04 /pmc/articles/PMC3458890/ /pubmed/22863301 http://dx.doi.org/10.1186/1742-2094-9-186 Text en Copyright ©2012 Kyrkanides et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Kyrkanides, Stephanos
Brouxhon, Sabine M
Tallents, Ross H
Miller, Jen-nie H
Olschowka, John A
O’Banion, M Kerry
Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation
title Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation
title_full Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation
title_fullStr Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation
title_full_unstemmed Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation
title_short Conditional expression of human β-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation
title_sort conditional expression of human β-hexosaminidase in the neurons of sandhoff disease rescues mice from neurodegeneration but not neuroinflammation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458890/
https://www.ncbi.nlm.nih.gov/pubmed/22863301
http://dx.doi.org/10.1186/1742-2094-9-186
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