Quiescent adult neural stem cells are exceptionally sensitive to cosmic radiation

Abstract

Generation of new neurons in the adult brain, a process that is likely to be essential for learning, memory, and mood regulation, is impaired by radiation. Therefore, radiation exposure might have not only such previously expected consequences as increased probability of developing cancer, but might also impair cognitive function and emotional stability. Radiation exposure is encountered in settings ranging from cancer therapy to space travel; evaluating the neurogenic risks of radiation requires identifying the at-risk populations of stem and progenitor cells in the adult brain. Here we have used a novel reporter mouse line to find that early neural progenitors are selectively affected by conditions simulating the space radiation environment. This is reflected both in a decrease in the number of these progenitors in the neurogenic regions and in an increase in the number of dying cells in these regions. Unexpectedly, we found that quiescent neural stem cells, rather than their rapidly dividing progeny, are most sensitive to radiation. Since these stem cells are responsible for adult neurogenesis, their death would have a profound impact on the production of new neurons in the irradiated adult brain. Our finding raises an important concern about cognitive and emotional risks associated with radiation exposure.

VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis

“…4B). Briefly, a nestin-GFP reporter transgene marking both NSCs and intermediate progenitor cells (IPCs) (but not further downstream descendants) (37,38) was bred onto the VEGF-switchable system, and NSCs were identified in hippocampal sections as GFP + cells having their cell body embedded in the DG SGZ and their major branch extending toward the granule cell layer (GCL) and terminating with an arbor of dendrite-like branches [a morphology earning these slow-dividing cells the name of radial glia-like cells (RGLs)]. Quantification of RGLs in young (3 mo) and old (13 mo) mice confirmed an age-related decline in total NSC number (66,000 cells per cubic millimeter and 39,000 cells per cubic millimeter, respectively).…”

The proliferation of amplifying neural progenitor cells is impaired in the aging brain and restored by the mTOR pathway activation

“…NSCs in the adult hippocampus include quiescent neural stem cells (QNPs) and their progeny, active neural stem cells (ANPs) (Abla and Sanai, 2013;Ahn and Joyner, 2005;Ashton et al, 2012;Encinas et al, 2008;Mignone et al, 2004;Song et al, 2012). Morphologically, QNPs are distinguished by their triangular cell body residing in the subgranular zone (SGZ) and a single process, which crosses the granular cell layer and terminates in the molecular layer of the hippocampus (Encinas et al, 2008). ANPs are derived from QNPs through asymmetric division and are characterized by an oval-shaped cell body that runs horizontal to the SGZ and the absence of long processes like QNPs (Gao et al, 2009;Mignone et al, 2004).…”

Cyclic patterns of incidence rate for skin malignant melanoma: association with heliogeophysical activity

“…Plausible biophysical pathways for these cyclic non-photic HGA influences in the later appearance of SMM may be direct, with a predominantly local receipt of the impact by UV irradiation, solar protons or heavy-charged particles (Cucinotta and Durante, 2006;Encinas et al, 2008) on the epidermal, adnexal and dermal cells or cutaneous nerve endings. The direct effect may be targeted, acting upon the melanocytes and interfering with their melanocytic defence system (MDS) (Dimitrov et al, 2007), or it may firstly be spread, initially intermediated by the surrounding microenvironment (e.g., bystander effect, skin neuroendocrine system (Slominski, 2005) signalling, and adjacent skin neuro-immunity impairment).…”

“…It is interesting that during the declining phase of the 11-year solar cycle, coronal activity is reaching a peak causing geomagnetic disturbances near the Earth orbit (for example, an intense storm can result from the superposition of two successive moderate storms driven by two successive structures in the solar wind) (Kamide, 2003). The latter effects may interfere not only with the Schumann frequencies and provoke carcinogenic stimuli (e.g., via the LF resonance with brain waives) but may also intermodulate with other cyclic cosmic influences (e.g., galactic cosmic rays, solar proton flux) that have also been related to increased cancer risk (Cucinotta and Durante, 2006) or sensitivity of quiescent neural stem cells (Encinas et al, 2008). These impacts and mechanisms could be linked not only to SMM appearance but together with environmental light effects and melatonin disturbances, to breast (Srinivasan et al, 2008) or other solid cancer occurrences as well.…”