Loss of neurofibromin in the leptomeningeal astroglial heterotopia of NF-1.
Neurofibromin, the protein product of the neurofibromatosis type 1 (NF-1) gene, has important roles in tumor suppression or normal embryogenesis. Cerebellar leptomeningeal astroglial heterotopia (LAH) is a proliferation of heterotopic astroglial cells and fibers in the cerebellar leptomeninges, which is characteristically demonstrated in the NF-1 patients. In this study, neurofibromin expression was investigated in NF-1 and non-NF-1 human tissues, especially in the cerebellum of NF-1 patients. Neurofibromin was found by immunoblotting in the CNS but not in the heart, liver, and kidney. Immunohistochemistry in the normal areas of the brains with NF-1 demonstrated neurofibromin immunoreactivity as did the brains of unaffected controls. Cerebellar LAH showed no neurofibromin immunoreactivity. The results of this study suggest that neurofibromin expression remains unchanged in the nonproliferated region of the CNS of the NF-1 patient but changes occur in the abnormally proliferated region, resulting in cerebellar LAH. Loss of neurofibromin may result in the excessive migration and growth of astrocytes in the early fetal period.
Kato
M
M
Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Mizuguchi
M
M
Hattori
S
S
Nakamura
S
S
Takashima
S
S
D000293:Adolescent; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002526:Cerebellar Diseases / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D025542:Neurofibromin 1; D011506:Proteins / Q000378:metabolism*
D025542:Neurofibromin 1; D011506:Proteins