Ionizing radiation-induced apoptosis of proliferating stem cells in the dentate gyrus of the adult rat hippocampus

Peißner, Wolfgang; Köcher, Martin; Treuer, Harald; Gillardon, Frank

doi:10.1016/s0169-328x(99)00170-9

Cited by 191 publications

(127 citation statements)

References 36 publications

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“…The IR is not truly unilateral, because considerable secondary radiation is scattered into the contralateral hemisphere, as judged by the dose-dependent appearance of injury markers. It has been demonstrated that the cells in the SVZ 31 and the SGZ 32,33 of the adult brain undergo apoptosis following ionizing radiation. Moreover, the size of the SVZ in adult rats reflects the number of proliferating cells, indicating that it is a good marker of SVZ precursor proliferation.…”

Section: Discussionmentioning

confidence: 99%

Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition

et al. 2004

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One hemisphere of postnatal day 8 (P8) rats or P10 mice was irradiated with a single dose of 4-12 Gy, and animals were killed from 2 h to 8 weeks after irradiation (IR). In the subventricular zone (SVZ) and the granular cell layer (GCL) of the dentate gyrus, harboring neural and other progenitor cells, nitrosylation and p53 peaked 2-12 h after IR, followed by markers for active caspase-3, apoptosis-inducing factor and TUNEL (6-24 h). Ki67-positive (proliferating) cells had disappeared by 12 h and partly reappeared by 7 days post-IR. The SVZ and GCL areas decreased approximately 50% 7 days after IR. The development of white matter was hampered, resulting in 50-70% less myelin basic protein staining. Pretreatment with erythropoietin did not confer protection against IR. Caspase inhibition by overexpression of XIAP prevented caspase-9 and caspase-3 activation but not cell death, presumably because of increased caspase-independent cell death.

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Section: Discussionmentioning

confidence: 99%

Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition

et al. 2004

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“…Recent reports have shown a higher incidence of cell death in proliferative zone of brain containing neural progenitors (Blaschke et al, 1996;Thomaidou et al, 1997;Rakic and Zecevic, 2000). Ionizing radiation has been shown to induce apoptosis of neural progenitors in fetal (D'SaEipper et al, 2001) and adult brain at much lower dose than needed to affect radioresistant neurons and glia (Peissner et al, 1999;Tada et al, 2000). Therefore, to analyse apoptotic processes affecting neural progenitors, we investigated the effects of g-radiation-induced DNA damages in highly enriched primary cultures.…”

Section: Discussionmentioning

confidence: 99%

“…Such mechanisms could be involved in neural progenitor response to various stresses affecting the developing brain or in the course of diverse brain pathologies, including neurodegenerative diseases and cancer. They may play a crucial role in the radio-induced impairment of neurogenesis that has been proposed to explain, in part, the progressive learning and memory deficits frequently observed in adult and children who receive radiotherapy involving the brain (Peissner et al, 1999;Tada et al, 2000;Monje and Palmer, 2003).…”

Section: Involvement Of Fas In Radiation-induced Apoptosis Of Neural mentioning

confidence: 99%

Involvement of p53 and Fas/CD95 in murine neural progenitor cell response to ionizing irradiation

et al. 2004

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We investigated the role of tumor suppressor p53 and Fas (CD95/APO-1), a member of the tumor necrosis factor receptor family, in neural progenitors response to cirradiation exposure. Telencephalic cells were obtained from wild-type C57Bl/6, or p53À/À or fasÀ/À, 15-dayold mouse embryos. They were cultured in conditions allowing neural progenitors to form proliferating clusters (neurospheres). A 2 Gy c-irradiation induced a G1 cell cycle arrest and triggered apoptosis in wild-type neural progenitor cultures in correlation with an enhanced expression of p53 and of its downstream target p21 WAF1 , both of them acquiring a nuclear localization. These effects did not occur in p53À/À neural progenitors demonstrating the central role played by p53 in their response to ionizing radiation. Furthermore, the monoclonal antibody Jo2 directed against Fas induced apoptosis of wild type but not of fasÀ/À neural progenitors, indicating the existence of a functional Fas signaling pathway in neural progenitors. Ionizing radiation induced an increase of Fas membrane expression related to a p53-dependent increase of fas mRNA expression in wild-type neural progenitors. Moreover, fasÀ/À neural progenitors exhibited delayed radiation-induced apoptosis compared to wild-type cells. Therefore, these findings establish a role for Fas/CD95 related to p53 in the response of neural progenitors to c-radiation exposure. Similar mechanisms could be triggered in neural progenitors in case of different stresses during brain development or in the course of various diseases affecting the adult brain.

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“…Treatment with a toxin for proliferating cells, the DNA methylating agent methylazoxymethanol acetate (MAM), reduced the number of newly generated cells in the DG without impairing overall health. Ionizing irradiation of the adult hippocampus also caused deletion of proliferating cells in the DG, leaving other cells apparently unchanged [62]. The effect of radiation was dose dependent, with cell death in the proliferating cells occurring within 3 to 6 hours after treatment, and lasted at least up to 120 days after irradiation [63].…”

Section: Potential Involvement Of Adult Neurogenesis In Learning and mentioning

confidence: 99%

Adult Neurogenesis and Hippocampal Memory Function: New Cells, More Plasticity, New Memories?

Kitabatake

Sailor

Ming

et al. 2007

Neurosurgery Clinics of North America

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Memory consists of several separate entities that depend on various brain systems [1]. Clinical and behavioral evidence suggests that the hippocampus and the surrounding anatomically associated regions serve a critical role in learning and memory [2]. In the 1960s, the outlines of the essential neural substrates of memory were gradually elucidated based on analyzing the effects of therapeutic surgical lesions of the bilateral medial temporal lobes to suppress uncontrollable epilepsy in a patient [3]. Although the operation was effective in controlling the patient's epilepsy, one unexpected consequence was that he became profoundly amnesic while retaining his intelligence and perceptual and motor functions. Similar cases were also seen in other patients with damage to the hippocampal formation and surrounding medial temporal lobe structures [4]. These individuals had severe amnesia for episodic events, although other forms of learning and memory-semantic, perceptual, procedural, and simple forms of conditioning-were spared. It is now believed that the hippocampal formation has a central role in declarative memory, the ability to recollect everyday facts and events consciously [5]. The unique anatomy, electrophysiologic characteristics, and key roles in memory formation have made the hippocampus an attractive target of research for neuroscientists.For decades, it was believed that neurogenesis only occurred during embryonic stages in the mammalian central nervous system (CNS), making the brain one of the few mammalian organs incapable of replenishing its functional cell population throughout life [6]. In the 1960s, seminal studies by Altman and Das [7][8][9] provided the first evidence that new neurons were generated in the postnatal mammalian brain. In 1992, Reynolds and Weiss [10] isolated multipotent neural stem/progenitor cells (NSCs) from the adult rodent brain and characterized them in vitro. Studies in the 1990s confirmed that, contrary to long-held dogma, NSCs reside in the adult CNS and active neurogenesis occurs in discrete regions of the adult brain across various mammalian species, including mice, rats, monkeys, and humans [11][12][13][14]. Only recently has it been recognized that adult neurogenesis replicates the complex process of neuronal development to generate functionally integrated new neurons ( Fig. 1) [15][16][17]. A role for these postnatally generated cells in learning was first suggested by Altman and Das in the 1960s [7-9,18]. Later, Nottebohm [19] directly tested the role of * Corresponding author: shongju1@jhmi.edu (H. Song). HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript adult-generated neurons in song learning in birds. Subsequent work in rodents has led to the idea that adult neurogenesis is important for learning and memory of spatial information.The discovery of adult neurogenesis has generated significant interest, especially in regard to the hippocampus, not only for neuroscientists but for physicians who are engaged in treating various ...

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Ionizing radiation-induced apoptosis of proliferating stem cells in the dentate gyrus of the adult rat hippocampus

Cited by 191 publications

References 36 publications

Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition

Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition

Involvement of p53 and Fas/CD95 in murine neural progenitor cell response to ionizing irradiation

Adult Neurogenesis and Hippocampal Memory Function: New Cells, More Plasticity, New Memories?

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