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

Stephanos Kyrkanides; Sabine M. Brouxhon; Ross H. Tallents; Jen nie H. Miller; John A. Olschowka; M. K. O'Banion

doi:10.1186/1742-2094-9-186

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

Stephanos Kyrkanides, Sabine M. Brouxhon, Ross H. Tallents, Jen nie H. Miller, John A. Olschowka, M. K. O'Banion

Oral Health Science

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

This study evaluated whether GM₂ 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 GM₂ neuronal storage and neurodegeneration, brain inflammation persisted, including the presence of large numbers of reactive microglia/macrophages due to persisting GM₂ 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.

Original language	English
Article number	679
Journal	Journal of Neuroinflammation
Volume	9
DOIs	https://doi.org/10.1186/1742-2094-9-186
State	Published - Aug 4 2012

Bibliographical note

Funding Information:
We would like to thank Dr Carl Pinkert for his role as Director of the Transgenic Facility in the generation of the Thy1-HEXB transgenic mouse, as well as Dr Fayrouz Bazina for her assistance in the double immunofluorescence experiments. This work was funded in part by grant NS048339 from the National Institutes of Health.

Funding

We would like to thank Dr Carl Pinkert for his role as Director of the Transgenic Facility in the generation of the Thy1-HEXB transgenic mouse, as well as Dr Fayrouz Bazina for her assistance in the double immunofluorescence experiments. This work was funded in part by grant NS048339 from the National Institutes of Health.

Funders	Funder number
National Institutes of Health (NIH)
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01NS048339

Keywords

Mouse
Neuron
Sandhoff disease
Transgenic
β-hexosaminidase

ASJC Scopus subject areas

General Neuroscience
Immunology
Neurology
Cellular and Molecular Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/1742-2094-9-186

Cite this

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

abstract = "This study evaluated whether GM2 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 GM2 neuronal storage and neurodegeneration, brain inflammation persisted, including the presence of large numbers of reactive microglia/macrophages due to persisting GM2 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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author = "Stephanos Kyrkanides and Brouxhon, {Sabine M.} and Tallents, {Ross H.} and Miller, {Jen nie H.} and Olschowka, {John A.} and O'Banion, {M. K.}",

note = "Funding Information: We would like to thank Dr Carl Pinkert for his role as Director of the Transgenic Facility in the generation of the Thy1-HEXB transgenic mouse, as well as Dr Fayrouz Bazina for her assistance in the double immunofluorescence experiments. This work was funded in part by grant NS048339 from the National Institutes of Health.",

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AU - Kyrkanides, Stephanos

AU - Brouxhon, Sabine M.

AU - Tallents, Ross H.

AU - Miller, Jen nie H.

AU - Olschowka, John A.

AU - O'Banion, M. K.

N1 - Funding Information: We would like to thank Dr Carl Pinkert for his role as Director of the Transgenic Facility in the generation of the Thy1-HEXB transgenic mouse, as well as Dr Fayrouz Bazina for her assistance in the double immunofluorescence experiments. This work was funded in part by grant NS048339 from the National Institutes of Health.

PY - 2012/8/4

Y1 - 2012/8/4

N2 - This study evaluated whether GM2 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 GM2 neuronal storage and neurodegeneration, brain inflammation persisted, including the presence of large numbers of reactive microglia/macrophages due to persisting GM2 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.

AB - This study evaluated whether GM2 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 GM2 neuronal storage and neurodegeneration, brain inflammation persisted, including the presence of large numbers of reactive microglia/macrophages due to persisting GM2 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.

KW - Mouse

KW - Neuron

KW - Sandhoff disease

KW - Transgenic

KW - β-hexosaminidase

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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