PEDIATRICS LABORATORY RESEARCH

摘要: Diffuse intrinsic pontine glioma (DIPG) is the pediatric brain malignancy with the worst prognosis. Our group has found a strong mitogenic effect of neuronal activity on normal neural stem and glial precursor cells. Neuronal activity may have a similar mitogenic effect in the DIPG microenvironment. We thus hypothesize that an interaction between ventral pontine neurons and glioma cells is pivotal to DIPG growth. We have investigated neuron-glioma cell interactions in vitro and found that human DIPG cells preferentially migrate towards human cortical areas rich in mature neurons compared to other regions poor in mature neurons (eg white matter tracts and the walls lining the lateral ventricles). These data may explain the histopathological hallmark of perineuronal satellitosis in DIPG. To test the role of physiological neuronal activity on DIPG growth in the ventral pons of freely moving mice, we are employing in vivo optogenetic techniques in our well-established orthotopic DIPG xenograft models. Utilizing these in vivo optogenetic neuronal stimulation models we will present data describing the effect of neuronal activity on glioma in vivo. If proven, this concept of neuronal-activity dependent glioma growth could not only provide fundamental insight into the pathogenesis of DIPG and other gliomas but also elucidate novel therapeutic targets for this devastating disease.