Tuberous sclerosis complex a paradigm for studying adult neurogenesis and brain tumors

Abstract

Tuberous sclerosis complex (TSC) is a relatively rare genetic disease characterized by the formation of benign tumors or hamartomas in multiple organs. The tumors are noninvasive and rarely transform to metastatic lesions. TSC is an autosomal dominant disorder that results from mutations in the TSC1 or TSC2 genes. Neurologically, individuals with TSC have severe complications, including refractory seizures, autism, mental retardation, learning difficulties, and changes in behavior. Tubers in the cerebral cortex, subependymal nodules (SENs) along the lateral walls of the lateral ventricles, and subependymal giant cell (GC) astrocytomas are characteristic brain lesions in patients with TSC. Astrocytic-like cells immunopositive for both glial and neuronal markers, dysplastic neurons (DNs), and GCs immunopositive for nestin and vimentin, as well as for proliferation markers such as proliferating nuclear cell antigen (PCNA) and Ki-67, are histological hallmarks of the disease. DNs and GCs retain their ability to re-enter the cell cycle and are immunopositive for markers of neural progenitor and stem cells. Neurogenesis occurs in the adult brain of mammals, particularly in the hippocampus and subventricular zone (SVZ). In the SVZ, newly generated neuronal cells migrate along the ventricle and a SVZ origin for brain tumors in the adult brain have been reported. These brain tumors express markers of neural progenitor and stem cells. The study of analogies and differences between SENs in TSC, neurogenesis in the SVZ, and tumors in the adult brain would reveal clues on the development and origin of SENs and brain tumors. Keywords: Epilepsy, Cancer, Drug, Disease, Neural stem cells, Rapamycin, Therapy, Tumor DOI:10.5055/jndr.2013.0012