Exp Mol Med.  2006 Aug;38(4):348-356.

Downregulation of neurotrophic factors in the brain of a mouse model of Gaucher disease: implications for neuronal loss in Gaucher disease

• Kim EY
• Hong YB
• Go SH
• Lee B
• Jung SC

Abstract

Gaucher disease is a glycosphingolipid storage disease caused by deficiency of glucocerebrosidase, resulting in the accumulation of glucosylceramide in lysosomes. The neuronopathic forms of this disease are associated with neuronal loss and neurodegeneration. However, the pathophysiological mechanisms leading to prenatal and neonatal death remain uncharacterized. To investigate brain dysfunction in Gaucher disease, we studied the effects of neurotrophic factors during development in a mouse model of Gaucher disease. The expression of brain-derived neurotrophic factor and nerve growth factor was reduced in the cerebral cortex, brainstem, and cerebellum of Gaucher mice, compared with that in wild-type mice. Extracellular signal-regulated kinase (ERK) 1/2 expression was downregulated in neurons from Gaucher mice and correlated with a decreased number of neurons. These results suggest that a reduction in neurotrophic factors could be involved in neuronal loss in Gaucher disease.

Keyword

brain; brain-derived neurotrophic factor; Gaucher disease; glucosylceramidase; nerve growth factor; neurons

MeSH Terms

Signal Transduction
Neurons/*metabolism
Nerve Growth Factors/*metabolism
Models, Animal
Mice, Inbred C57BL
Mice
MAP Kinase Signaling System/physiology
Gaucher Disease/*metabolism/pathology
Down-Regulation
Cells, Cultured
Cell Survival
Brain/*metabolism
Animals