Brain and nervous system cancers in children represent the second most common neoplasia after leukemia. Radiotherapy plays a significant role in cancer treatment; however, the use of such therapy is not without devastating side effects. The impact of radiation-induced damage to the brain is multifactorial, but the damage to neural stem cell populations seems to play a key role. The brain contains pools of regenerative neural stem cells that reside in specialized neurogenic niches and can generate new neurons. In this review, we describe the advances in radiotherapy techniques that protect neural stem cell compartments, and subsequently limit and prevent the occurrence and development of side effects. We also summarize the current knowledge about neural stem cells and the molecular mechanisms underlying changes in neural stem cell niches after brain radiotherapy. Strategies used to minimize radiation-related damages, as well as new challenges in the treatment of brain tumors are also discussed.

a b s t r a c t DISP3 (PTCHD2), a sterol-sensing domain-containing protein, is highly expressed in neural tissue but its role in neural differentiation is unknown. In the present study we used a multipotent cerebellar progenitor cell line, C17.2, to investigate the impact of DISP3 on the proliferation and differentiation of neural precursors. We found that ectopically expressed DISP3 promotes cell proliferation and alters expression of genes that are involved in tumorigenesis. Finally, the differentiation profile of DISP3-expressing cells was altered, as evidenced by delayed expression of neural specific markers and a reduced capacity to undergo neural differentiation.

Radiotherapy plays a significant role in brain cancer treatment; however, the use of this therapy is often accompanied by neurocognitive decline that is, at least partially, a consequence of radiation-induced damage to neural stem cell populations. Our findings describe features that define the response of neural stem cells (NSCs) to ionizing radiation. We investigated the effects of irradiation on neural stem cells isolated from the ventricular-subventricular zone of mouse brain and cultivated in vitro. Our findings describe the increased transcriptional activity of p53 targets and proliferative arrest after irradiation. Moreover, we show that most cells do not undergo apoptosis after irradiation but rather cease proliferation and start a differentiation program. Induction of differentiation and the demonstrated potential of irradiated cells to differentiate into neurons may represent a mechanism whereby damaged NSCs eliminate potentially hazardous cells and circumvent the debilitating consequences of cumulative DNA damage.