Cerebellar pathology and motor deficits in the palmitoyl protein thioesterase 1-deficient mouse.

Abstract

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 PPT1-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 S100beta 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.

• Authors: Shannon L Macauley, David F Wozniak, Catherine Kielar, Yun Tan, Jonathan D Cooper, Mark S Sands
• Journal: Experimental neurology (Exp Neurol) Vol. 217 Issue 1 Pg. 124-35 (May 2009) ISSN: 1090-2430 [Electronic] United States
• PMID: 19416667 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Excitatory Amino Acid Transporter 1
• Excitatory Amino Acid Transporter 2
• Glial Fibrillary Acidic Protein
• Nerve Growth Factors
• S100 Calcium Binding Protein beta Subunit
• S100 Proteins
• Slc1a3 protein, mouse
• Thiolester Hydrolases
• palmitoyl-protein thioesterase

Topics

• Age Factors
• Animals
• Apoptosis (genetics)
• Astrocytes (metabolism, pathology)
• Cerebellum (pathology, physiopathology)
• Disease Models, Animal
• Excitatory Amino Acid Transporter 1 (metabolism)
• Excitatory Amino Acid Transporter 2 (metabolism)
• Glial Fibrillary Acidic Protein (metabolism)
• In Situ Nick-End Labeling (methods)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microglia (metabolism, pathology)
• Motor Activity (genetics)
• Movement Disorders (genetics, physiopathology)
• Nerve Degeneration (pathology)
• Nerve Growth Factors (metabolism)
• Neuronal Ceroid-Lipofuscinoses (genetics, physiopathology)
• Neurons (metabolism, pathology)
• Organ Size (genetics)
• S100 Calcium Binding Protein beta Subunit
• S100 Proteins (metabolism)
• Staining and Labeling (methods)
• Thiolester Hydrolases (deficiency)