Downregulation of neurotrophic factors in the brain of a mouse model of Gaucher disease; implications for neuronal loss in Gaucher disease.
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.
Kim
Eun Young
EY
Department of Biomedical Sciences, National Institute of Health, Seoul 122-701, Korea.
Hong
Young Bin
YB
Go
Sang Hee
SH
Lee
Beobyi
B
Jung
Sung-Chul
SC
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D015536:Down-Regulation; D005776:Gaucher Disease / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D015398:Signal Transduction
D009414:Nerve Growth Factors