Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis
The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are fatal inherited neurodegenerative diseases. Sheep affected with the CLN6 form provide a valuable model to investigate underlying disease mechanisms from preclinical stages. Excitatory neuron loss in these sheep is markedly regional, local...
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doaj-71c07d56d650485f89b3b6a1fed309f02021-03-20T04:56:02ZengElsevierNeurobiology of Disease1095-953X2008-10-013215065Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosisManfred J. Oswald0David N. Palmer1Graham W. Kay2Karen J. Barwell3Jonathan D. Cooper4Agriculture and Life Sciences Division, PO Box 84, Lincoln University, Lincoln 7647, New Zealand; Department of Neuroscience and Centre for the Cellular Basis of Behaviour, Pediatric Storage Disorders Laboratory, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UKAgriculture and Life Sciences Division, PO Box 84, Lincoln University, Lincoln 7647, New Zealand; Corresponding author. Fax: +64 3 325 3851.Agriculture and Life Sciences Division, PO Box 84, Lincoln University, Lincoln 7647, New ZealandAgriculture and Life Sciences Division, PO Box 84, Lincoln University, Lincoln 7647, New ZealandDepartment of Neuroscience and Centre for the Cellular Basis of Behaviour, Pediatric Storage Disorders Laboratory, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UKThe neuronal ceroid lipofuscinoses (NCLs, Batten disease) are fatal inherited neurodegenerative diseases. Sheep affected with the CLN6 form provide a valuable model to investigate underlying disease mechanisms from preclinical stages. Excitatory neuron loss in these sheep is markedly regional, localized early reactive changes accurately predicting neuron loss and subsequent symptom development. This investigation of GABAergic interneuron loss revealed similar regional effects that correlate with symptoms.Loss of parvalbumin positive neurons from the affected cortex was apparent at four months and became profound by 19 months, as was somatostatin positive neuron loss to a lesser extent. Conversely calbindin and neuropeptide Y positive neurons were relatively preserved and calretinin staining temporarily increased. Staining of subcortical regions was more intense but subcortical architecture remained relatively intact. Discrete subcortical changes followed from cortical changes in interconnected regions. These data highlight cellular location and interconnectivity as the major determinants of neuron survival, rather than phenotype.http://www.sciencedirect.com/science/article/pii/S0969996108001307Batten diseaseNeuronal ceroid lipofuscinosisCLN6GABAergic interneuronsOvine modelLysosomal storage disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Manfred J. Oswald David N. Palmer Graham W. Kay Karen J. Barwell Jonathan D. Cooper |
spellingShingle |
Manfred J. Oswald David N. Palmer Graham W. Kay Karen J. Barwell Jonathan D. Cooper Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis Neurobiology of Disease Batten disease Neuronal ceroid lipofuscinosis CLN6 GABAergic interneurons Ovine model Lysosomal storage disease |
author_facet |
Manfred J. Oswald David N. Palmer Graham W. Kay Karen J. Barwell Jonathan D. Cooper |
author_sort |
Manfred J. Oswald |
title |
Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis |
title_short |
Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis |
title_full |
Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis |
title_fullStr |
Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis |
title_full_unstemmed |
Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis |
title_sort |
location and connectivity determine gabaergic interneuron survival in the brains of south hampshire sheep with cln6 neuronal ceroid lipofuscinosis |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2008-10-01 |
description |
The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are fatal inherited neurodegenerative diseases. Sheep affected with the CLN6 form provide a valuable model to investigate underlying disease mechanisms from preclinical stages. Excitatory neuron loss in these sheep is markedly regional, localized early reactive changes accurately predicting neuron loss and subsequent symptom development. This investigation of GABAergic interneuron loss revealed similar regional effects that correlate with symptoms.Loss of parvalbumin positive neurons from the affected cortex was apparent at four months and became profound by 19 months, as was somatostatin positive neuron loss to a lesser extent. Conversely calbindin and neuropeptide Y positive neurons were relatively preserved and calretinin staining temporarily increased. Staining of subcortical regions was more intense but subcortical architecture remained relatively intact. Discrete subcortical changes followed from cortical changes in interconnected regions. These data highlight cellular location and interconnectivity as the major determinants of neuron survival, rather than phenotype. |
topic |
Batten disease Neuronal ceroid lipofuscinosis CLN6 GABAergic interneurons Ovine model Lysosomal storage disease |
url |
http://www.sciencedirect.com/science/article/pii/S0969996108001307 |
work_keys_str_mv |
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