While it is widely accepted that HZE irradiation decreases neurogenesis, only one study has examined the impact of 12C on DG neurogenesis. Even though heavy particle therapy for cancer treatment is typically provided in a focal beam and HZE particle work relevant to space radiation is typically provided as whole-body irradiation, the underlying mechanisms of how 12C disrupts brain and behavior in the context of space travel is likely to also be relevant to heavy particle therapy. Specifically, 12C is a good candidate to replace X-irradiation as the ability to target this heavy radiation beam enables sparing of the normal tissue surrounding a tumor. This is somewhat surprising given that 12C irradiation has emerged as a potential cancer treatment.

When compared to the many HZE particles that comprise space radiation, carbon ( 12C) has received far less attention in regard to its impact on DG neurogenesis. As HZE particle exposure is an unavoidable aspect of deep space missions, it is important to gain a complete understanding of how exposure to distinct HZE particles influences DG neurogenesis. Functionally, HZE exposure has been linked to accelerated aging, anxiety-like symptoms, spatial learning and memory deficits, and decreased operant responses in laboratory animals, all of which might be related to decreased DG neurogenesis. Of note, the high-charge and high-energy (HZE) particles-such as 56Fe and 28Si-that comprise cosmic radiation have been extensively studied for their ability to impact DG neurogenesis in laboratory animals, with most work reporting a negative impact of space radiation on indices of neurogenesis. We now know a great deal about the function and regulation of adult DG neurogenesis, including its role in memory and mood, its regulation by oxidative stress, and its exceptional sensitivity to types of radiation. Over fifty years ago, Altman and Das showed new neurons are generated in the adult mammalian hippocampal dentate gyrus (DG), thus disproving the long-standing belief that neurogenesis ceases at birth.

These data underscore the ability of neurogenesis in the mouse brain to recover from the detrimental effect of 12C exposure. IRR mice had fewer surviving BrdU+ cells versus Sham mice, suggesting decreased cell survival, but there was no difference in BrdU+ cell survival rate when compared within treatment and across time point. For the Long-Term time point, IRR and Sham mice had similar Ki67+ and DCX+ cell numbers, suggesting restoration of proliferation and immature neurons 3 months post- 12C irradiation. For the Short-Term time point, IRR mice had fewer Ki67, BrdU, and doublecortin (DCX) immunoreactive (+) cells versus Sham mice, indicating decreased proliferation (Ki67, BrdU) and immature neurons (DCX). 22 h post-irradiation and brains were harvested 2 h (Short-Term) or three months (Long-Term) later for stereological analysis indices of dentate gyrus neurogenesis. To birthdate dividing cells, mice received BrdU i.p. To address this knowledge gap, male mice (9вЂ“11 weeks of age) were exposed to whole-body 12C irradiation 100 cGy (IRR 1000 MeV/n 8 kEV/Вµm) or Sham treatment. However, much about 12CвЂ™s influence on neurogenesis remains unknown, including the time course of its impact on neurogenesis.

While exposure to most HZE particles decreases neurogenesis in the hippocampus-a brain structure important in memory-prior work suggests that 12C does not. High-charge and -energy (HZE) particles comprise space radiation and they pose a challenge to astronauts on deep space missions.

Stereology for dummies