Downregulation of neurotrophic factors in the brain of a mouse model of Gaucher disease: implications for neuronal loss in Gaucher disease.
- Author:
Eun Young KIM
1
;
Young Bin HONG
;
Sang Hee GO
;
Beoby LEE
;
Sung Chul JUNG
Author Information
1. Department of Biomedical Sciences, National Institute of Health Seoul, 122-701, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
brain;
brain-derived neurotrophic factor;
Gaucher disease;
glucosylceramidase;
nerve growth factor;
neurons
- MeSH:
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
- From:Experimental & Molecular Medicine
2006;38(4):348-356
- CountryRepublic of Korea
- Language:English
-
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.
