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Non-nuclear histone H1 is upregulated in neurones and astrocytes in prion and Alzheimer's diseases but not in acute neurodegeneration

Non-nuclear histone H1 is upregulated in neurones and astrocytes in prion and Alzheimer's diseases but not in acute neurodegeneration
Non-nuclear histone H1 is upregulated in neurones and astrocytes in prion and Alzheimer's diseases but not in acute neurodegeneration
A non-nuclear isoform of histone H1 is constitutively expressed in neurones. This protein is the major lipopolysaccharide (LPS)-binding protein in the brain. Since the major systemic LPS-binding protein is released in the liver and is an acute phase reactant, we were interested to learn whether this novel CNS histone showed altered expression following neuronal injury. We have therefore examined the changes in the expression of this molecule in acute neuronal injury and in two neurodegenerative pathologies, murine scrapie and Alzheimer's disease. No upregulation or change in H1 staining was observed in acute neurodegeneration induced by the intrastriatal injection of the glutamate antagonist N-methyl d-aspartic acid. In contrast, Western blotting indicated that histone H1 is upregulated in the brains of mice with clinical signs of scrapie. Immunohistochemistry revealed that in the regions of pathology there was increased staining for histone H1 in the neurones and the surrounding neuropil. Cells with an astrocytic appearance were also seen to stain positively for H1 but only in the regions of pathology. Immunofluorescent double staining for glial fibrillary acid protein (GFAP) and histone H1 confirmed that these cells were indeed astrocytes. Alzheimer's disease brain also showed an increase in the neuronal and astrocytic staining but only in regions of pathology. The function of histone in the CNS is unknown but the data presented here demonstrate an upregulation in areas of neuronal degeneration, which indicates that it may be involved in disease pathogenesis.
alzheimer's disease, astrocytes, histone H1, neurodegeneration, neurones, prion disease, scrapie
0305-1846
425-432
Bolton, S.J.
e7242fa7-c2ed-4b19-a9f0-8b95acfe38c7
Russelakis-Carneiro, M.
51e89362-f101-44e9-b304-4e5ba721ec87
Betmouni, S.
9ac667ca-aa03-4d8e-b7b2-ce6fc34d1121
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Bolton, S.J.
e7242fa7-c2ed-4b19-a9f0-8b95acfe38c7
Russelakis-Carneiro, M.
51e89362-f101-44e9-b304-4e5ba721ec87
Betmouni, S.
9ac667ca-aa03-4d8e-b7b2-ce6fc34d1121
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4

Bolton, S.J., Russelakis-Carneiro, M., Betmouni, S. and Perry, V.H. (1999) Non-nuclear histone H1 is upregulated in neurones and astrocytes in prion and Alzheimer's diseases but not in acute neurodegeneration. Neuropathology and Applied Neurobiology, 25 (5), 425-432. (doi:10.1046/j.1365-2990.1999.00171.x).

Record type: Article

Abstract

A non-nuclear isoform of histone H1 is constitutively expressed in neurones. This protein is the major lipopolysaccharide (LPS)-binding protein in the brain. Since the major systemic LPS-binding protein is released in the liver and is an acute phase reactant, we were interested to learn whether this novel CNS histone showed altered expression following neuronal injury. We have therefore examined the changes in the expression of this molecule in acute neuronal injury and in two neurodegenerative pathologies, murine scrapie and Alzheimer's disease. No upregulation or change in H1 staining was observed in acute neurodegeneration induced by the intrastriatal injection of the glutamate antagonist N-methyl d-aspartic acid. In contrast, Western blotting indicated that histone H1 is upregulated in the brains of mice with clinical signs of scrapie. Immunohistochemistry revealed that in the regions of pathology there was increased staining for histone H1 in the neurones and the surrounding neuropil. Cells with an astrocytic appearance were also seen to stain positively for H1 but only in the regions of pathology. Immunofluorescent double staining for glial fibrillary acid protein (GFAP) and histone H1 confirmed that these cells were indeed astrocytes. Alzheimer's disease brain also showed an increase in the neuronal and astrocytic staining but only in regions of pathology. The function of histone in the CNS is unknown but the data presented here demonstrate an upregulation in areas of neuronal degeneration, which indicates that it may be involved in disease pathogenesis.

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More information

Published date: 1 October 1999
Keywords: alzheimer's disease, astrocytes, histone H1, neurodegeneration, neurones, prion disease, scrapie

Identifiers

Local EPrints ID: 56233
URI: http://eprints.soton.ac.uk/id/eprint/56233
ISSN: 0305-1846
PURE UUID: 1c27f6d3-8beb-4bda-93c2-5dfa74757af2

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Date deposited: 21 Aug 2008
Last modified: 15 Mar 2024 11:00

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Contributors

Author: S.J. Bolton
Author: M. Russelakis-Carneiro
Author: S. Betmouni
Author: V.H. Perry

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