myelin-basic-protein and Tuberous-Sclerosis

Tuberous sclerosis (TSC) is an autosomal dominant syndrome that is linked to two genetic loci: TSC1 (9q34) and TSC2 (16p13). Brain manifestations such as cortical tubers and subependymal hamartoma/giant cell astrocytomas are major causes of TSC-related morbidity. In this study, we describe the central nervous system involvement in a unique rodent model of tuberous sclerosis. The Eker rat carries a spontaneous germline mutation of the TSC2 gene and is predisposed to multiple neoplasia. In a series of 45 adult Eker carriers (TSC2 +/-), three types of focal intracranial lesions were found, of which the subependymal and subcortical hamartomas were most prevalent (65%). There exist remarkable phenotypic similarities between the Eker rat and human subependymal lesions. Our study indicates that the predominant cellular phenotype of the subependymal hamartomas is astroglial and suggests that the neuronal contribution within these lesions is, in part, the result of pre-existing myelinated axons. The hamartomas did not show evidence of loss of the wild-type TSC2 allele; it remains to be determined whether TSC2 inactivation is necessary for their pathogenesis. This genetically-defined rodent model may be useful in elucidating the molecular and developmental basis of the subependymal giant cell astrocytoma in humans.

Topics: Animals; Astrocytes; Brain Diseases; Calbindins; Disease Models, Animal; Ependyma; Glial Fibrillary Acidic Protein; Hamartoma; Immunohistochemistry; Loss of Heterozygosity; Myelin Basic Protein; Neurofilament Proteins; Rats; Rats, Inbred F344; Rodent Diseases; S100 Calcium Binding Protein G; Tuberous Sclerosis; Tubulin

Two cases of TS associated with brain tumors had severe psychomotor retardation and early onset of long-term intractable convulsions, compared with cases without tumors. In one case, the tumor was partially cystic and progressed rapidly. Immunohistochemical studies of neuron specific enolase, glial fibrillary acidic protein and myelin basic protein revealed differences in positivity between cell types and between cases. These results suggested that the origin of the tumor cells could be variably differentiated cells.

Topics: Adolescent; Adult; Astrocytoma; Brain Neoplasms; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Myelin Basic Protein; Phosphopyruvate Hydratase; Staining and Labeling; Tomography, X-Ray Computed; Tuberous Sclerosis

Subependymal giant cell astrocytomas associated with tuberous sclerosis were studied with immunostains for glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and neuron-specific enolase (NSE). Tumor tissue was composed of three forms of cells; polygonal, ovoid and fusiform. A polygonal form was large in size and contained a vesicular nucleus, a distinct nucleolus and scarce Nissl granules resembling a nerve cell. An ovoid cell was similar to a gemistocytic astrocyte. Glial fibers stained with PTAH were observed to surround the tumor cell cluster. Immunocytochemically the polygonal cells were GFAP-and NSE-positive, the ovoid cells were GFAP-, MBP- and NSE-positive, and the fusiform cells were sometimes GFAP- and NSE-positive. The origin of tumor cells remains controversial, either glial or neuronal. This tumor occurs commonly in the subependymal region where germinal matrix cells appear at the early developmental stage. These results suggest that subependymal giant cell astrocytoma could have the totipotential to differentiate to astrocytic, oligodendrocytic as well as neuronal cells.

Topics: Astrocytoma; Brain Neoplasms; Cell Transformation, Neoplastic; Child; Female; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Male; Myelin Basic Protein; Phosphopyruvate Hydratase; Tuberous Sclerosis