The brain undergoes ionizing radiation (IR) exposure in many clinical situations, particularly during radiotherapy for malignant brain tumors. Cranial radiation therapy is related with the hazard of long-term neurocognitive decline. The detrimental ionizing radiation effects on the brain closely correlate with age at treatment, and younger age associates with harsher deficiencies. Radiation has been shown to induce damage in several cell populations of the mouse brain. Indeed, brain exposure causes a dysfunction of the neurogenic niche due to alterations in the neuronal and supporting cell progenitor signaling environment, particularly in the hippocampus—a region of the brain critical to memory and cognition. Consequent deficiencies in rates of generation of new neurons, neural differentiation and apoptotic cell death, lead to neuronal deterioration and lasting repercussions on neurocognitive functions. Besides neural stem cells, mature neural cells and glial cells are recognized IR targets. We will review the current knowledge about radiation-induced damage in stem cells of the brain and discuss potential treatment interventions and therapy methods to prevent and mitigate radiation related cognitive decline.

In 2011, the International Commission on Radiological Protection (ICRP) recommended reducing the occupational equivalent dose limit for the lens of the eye from 150 mSv/year to 20 mSv/year, averaged over five years, with no single year exceeding 50 mSv. With this recommendation, several important assumptions were made, such as lack of dose rate effect, classification of cataracts as a tissue reaction with a dose threshold at 0.5 Gy, and progression of minor opacities into vision-impairing cataracts. However, although new dose thresholds and occupational dose limits have been set for radiation-induced cataract, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological and mechanistic evidence at doses under 2 Gy. Since the release of the 2011 ICRP statement, the Multidisciplinary European Low Dose Initiative (MELODI) supported in April 2019 a scientific workshop that aimed to review epidemiological, clinical and biological evidence for radiation-induced cataracts. The purpose of this article is to present and discuss recent related epidemiological and clinical studies, ophthalmic examination techniques, biological and mechanistic knowledge, and to identify research gaps, towards the implementation of a research strategy for future studies on radiation-induced lens opacities. The authors recommend particularly to study the effect of ionizing radiation on the lens in the context of the wider, systemic effects, including in the retina, brain and other organs, and as such cataract is recommended to be studied as part of larger scale programs focused on multiple radiation health effects.

Acceleration of atherogenesis in ApoE / mice exposed to acute or low-dose-rate ionizing radiation Acceleration of atherogenesis in ApoE−/− mice exposed to acute or low-dose-rate ionizing radiation

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite the progress of new treatments, the risk of recurrence, morbidity, and death remains significant and the long-term adverse effects in survivors are substantial. The fraction of cancer stem-like cells (CSCs) because of their self-renewal ability and multi-lineage differentiation potential is critical for tumor initiation, growth, and resistance to therapies. For the development of new CSC-targeted therapies, further in-depth studies are needed using enriched and stable MB-CSCs populations. This work, aimed at identifying the amount of CSCs in three available human cell lines (DAOY, D341, and D283), describes different approaches based on the expression of stemness markers. First, we explored potential differences in gene and protein expression patterns of specific stem cell markers. Then, in order to identify and discriminate undifferentiated from differentiated cells, MB cells were characterized using a physical characterization method based on a high-frequency dielectrophoresis approach. Finally, we compared their tumorigenic potential in vivo, through engrafting in nude mice. Concordantly, our findings identified the D283 human cell line as an ideal model of CSCs, providing important evidence on the use of a commercial human MB cell line for the development of new strategic CSC-targeting therapies.

Chronic inflammatory bowel disorders (IBD) are idiopathic diseases associated with altered intestinal permeability, which in turn causes an exaggerated immune response to enteric antigens in a genetically susceptible host. A rise in psych cognitive disorders, such as anxiety and depression, has been observed in IBD patients. We here report investigations on a model of chemically induced experimental colitis by oral administration of sodium dextran sulfate (DSS) in C57BL/6 mice. We investigate, in vivo, the crosstalk between the intestine and the brain, evaluating the consequences of intestinal inflammation on neuroinflammation and hippocampal adult neurogenesis. By using different DSS administration strategies, we are able to induce acute or chronic colitis, simulating clinical characteristics observed in IBD patients. Body weight loss, colon shortening, alterations of the intestinal mucosa and fecal metabolic changes in amino acids-, lipid- and thiamine-related pathways are observed in colitis. The activation of inflammatory processes in the colon is confirmed by macrophage infiltration and increased expression of the proinflammatory cytokine and oxidative stress marker (Il-6 and iNOS). Interestingly, in the hippocampus of acutely DSS-treated mice, we report the upregulation of inflammatory-related genes (Il-6, Il-1β, S-100, Tgf-β and Smad-3), together with microgliosis. Chronic DSS treatment also resulted in neuroinflammation in the hippocampus, indicated by astrocyte activation. Evaluation of stage-specific neurogenesis markers reveals deficits in the dentate gyrus after acute and chronic DSS treatments, indicative of defective adult hippocampal neurogenesis. Finally, based on a possible causal relationship between gut-related inflammation and brain cancer, we investigate the impact of DSS-induced colitis on oncogenesis, using the Ptch1^+/−/C57BL/6 mice, a well-established medulloblastoma (MB) mouse model, finding no differences in MB development between untreated and DSS-treated mice. In conclusion, in our experimental model, the intestinal inflammation associated with acute and chronic colitis markedly influences brain homeostasis, impairing hippocampal neurogenesis but not MB oncogenesis.