Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6)
The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are fatal inherited neurodegenerative diseases characterized by gross brain atrophy, blindness, and intracellular accumulation of lysosome-derived storage bodies. A CLN6 form in sheep is studied as a large animal model of the human diseases....
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| Format: | Article |
| Language: | English |
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Elsevier
2005-10-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996105000446 |
| _version_ | 1818560435695124480 |
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| author | Manfred J. Oswald David N. Palmer Graham W. Kay Stephen J.A. Shemilt Payam Rezaie Jonathan D. Cooper |
| author_facet | Manfred J. Oswald David N. Palmer Graham W. Kay Stephen J.A. Shemilt Payam Rezaie Jonathan D. Cooper |
| author_sort | Manfred J. Oswald |
| collection | DOAJ |
| description | The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are fatal inherited neurodegenerative diseases characterized by gross brain atrophy, blindness, and intracellular accumulation of lysosome-derived storage bodies. A CLN6 form in sheep is studied as a large animal model of the human diseases. This study describes neuropathological changes in brains from presymptomatic affected sheep. Activated astrocytes and focal clusters of activated microglia were present in outer layers of occipital and somatosensory cortical regions as early as 12 days of age, together with activated perivascular macrophages. Astrocytic activation and progressive transformation of microglia to brain macrophages preceded neurodegeneration and spread to different cortical areas, most prominently in regions associated with clinical symptoms. In contrast, storage body accumulation was much more evenly spread across regions. These data support suggestions that neurodegeneration and storage body accumulation may be independent manifestations of CLN6 mutation and indicate that glial cell activation may be an important mediator in pathogenesis. |
| first_indexed | 2024-12-14T00:38:25Z |
| format | Article |
| id | doaj.art-fdbd8ce641c14ebaa77d5f37b4203033 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-14T00:38:25Z |
| publishDate | 2005-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-fdbd8ce641c14ebaa77d5f37b42030332022-12-21T23:24:30ZengElsevierNeurobiology of Disease1095-953X2005-10-012014963Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6)Manfred J. Oswald0David N. Palmer1Graham W. Kay2Stephen J.A. Shemilt3Payam Rezaie4Jonathan D. Cooper5Agriculture and Life Sciences Division, Lincoln University, PO Box 84, Canterbury, New ZealandAgriculture and Life Sciences Division, Lincoln University, PO Box 84, Canterbury, New Zealand; Corresponding author. Fax +64 3 325 3851.Agriculture and Life Sciences Division, Lincoln University, PO Box 84, Canterbury, New ZealandPediatric Storage Disorders Laboratory and Departments of Neuropathology and Neuroscience, Institute of Psychiatry, King's College London, UKDepartment of Biological Sciences, The Open University, Milton Keynes, UKPediatric Storage Disorders Laboratory and Departments of Neuropathology and Neuroscience, Institute of Psychiatry, King's College London, UKThe neuronal ceroid lipofuscinoses (NCLs, Batten disease) are fatal inherited neurodegenerative diseases characterized by gross brain atrophy, blindness, and intracellular accumulation of lysosome-derived storage bodies. A CLN6 form in sheep is studied as a large animal model of the human diseases. This study describes neuropathological changes in brains from presymptomatic affected sheep. Activated astrocytes and focal clusters of activated microglia were present in outer layers of occipital and somatosensory cortical regions as early as 12 days of age, together with activated perivascular macrophages. Astrocytic activation and progressive transformation of microglia to brain macrophages preceded neurodegeneration and spread to different cortical areas, most prominently in regions associated with clinical symptoms. In contrast, storage body accumulation was much more evenly spread across regions. These data support suggestions that neurodegeneration and storage body accumulation may be independent manifestations of CLN6 mutation and indicate that glial cell activation may be an important mediator in pathogenesis.http://www.sciencedirect.com/science/article/pii/S0969996105000446AstrocytosisBatten diseaseBrain macrophagesFluorescentLysosomal storage diseaseMicroglia |
| spellingShingle | Manfred J. Oswald David N. Palmer Graham W. Kay Stephen J.A. Shemilt Payam Rezaie Jonathan D. Cooper Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6) Neurobiology of Disease Astrocytosis Batten disease Brain macrophages Fluorescent Lysosomal storage disease Microglia |
| title | Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6) |
| title_full | Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6) |
| title_fullStr | Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6) |
| title_full_unstemmed | Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6) |
| title_short | Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6) |
| title_sort | glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis cln6 |
| topic | Astrocytosis Batten disease Brain macrophages Fluorescent Lysosomal storage disease Microglia |
| url | http://www.sciencedirect.com/science/article/pii/S0969996105000446 |
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