期刊
EXPERIMENTAL NEUROLOGY
卷 217, 期 1, 页码 124-135出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2009.01.022
关键词
Batten disease; Lysosomal storage disease; Rotarod; Cerebellar mutant; Gliosis; Astrocytes; Silver degeneration staining; Neurodegeneration; GLAST; Glutamine synthetase
资金
- NIH [NS043105, NS41930, P30 NS057105]
- NRSA [NS056728]
Infantile neuronal ceroid lipofuscinosis (INCL, Infantile Batten Disease) is an inherited, neurodegenerative lysosomal storage disorder. INCL is the result of a CLN1 gene mutation leading to a deficiency in palmitoyl protein thioesterase 1 (PPT1) activity. Studies in the forebrain demonstrate the PM-deficient mouse (PPT1-/-) mimics the clinical symptoms and underlying pathology of INCL; however, little is known about changes in cerebellar function or pathology. In this study, we demonstrate Purkinje cell loss beginning at 3 months, which correlates with changes in rotarod performance. Concurrently, we observed an early stage reactive gliosis and a primary pathology in astrocytes, including changes in S100 beta and GLAST expression. Conversely, there was a late stage granule cell loss, microglial activation, and demyelination. This study suggests that neuronal-glial interactions are the core pathology in the PPT1-/- cerebellum. In addition, these data identify potential endpoints for use in future efficacy studies for the treatment of INCL (C) 2009 Elsevier Inc. All rights reserved.
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