ROS effects on neurodegeneration in Alzheimer’s disease and related disorders: on environmental stresses of ionizing radiation

Author: Manton K.G., Volovik S., Kulminski A.

Reference: Curr Alzheimer Res. — 2004. — Vol. 1, № 4. — 277–293.

Keywords: Alzheimer’s disease, CNS, ROS, Hiroshima, Nagasaki, Chernobyl, Ionizing radiation, ambiphilic, mitochondria, radionuclides, neurons, astrocytes, microglia

Abstract: Neurodegenerative processes associated with Alzheimer’s disease are complex and involve many CNS tissue types, structures and biochemical processes. Factors believed involved in these processes are generation of Reactive Oxygen Species (ROS), associated inflammatory responses, and the bio-molecular and genetic damage they produce. Since oxidative processes are essential to energy production, and to other biological functions, such as cell signaling, the process is not one of risk exposure, as for cigarettes and cancer, but one where normal physiological processes operate out of normal ranges and without adequate control. Thus, it is necessary to study the ambiphilicity that allows the same molecule (e.g., beta amyloid) to behave in contradictory ways depending upon the physiological microenvironment. To determine ways to study this in human populations we review evidence on the effects of an exogenous generator of ROS, ionizing radiation, in major population events with radionuclides (e.g., Hiroshima and Nagasaki; Chernobyl Reactor accident; environmental contamination in Chelyabinsk (South Urals) where plutonium was produced, and in the nuclear weapons test area in Semipalatinsk, Kazakhstan). The age evolution, and traits, of neurodegenerative processes in human populations in these areas, may help us understand how IR affects the CNS. After reviewing human population evidence, we propose a model of neurodegeneration based upon the complexity of CNS functions.

URL: http://www.ncbi.nlm.nih.gov/pubmed/15975057

Does ionizing radiation accelerate aging phenomena

Author: V. Bebeshko, D. Bazyka, K. Loganovsky et al.

Reference: Contributed papers to The International Conference “Twenty years after Chornobyl accident future outlook”, April 24–26, Kyiv, Ukraine. — Kyiv: HOLTEH, 2006. — P. 13–19.

Keywords: aging, DNA, immune function, nervous system effects

Abstract: Radiation accelerated aging might be a model of senescence in humans. Natural (normal) aging is a complex temporal process. Radiation is a phenomenon, which, by influencing cell structure and function, changes that process at the molecular and genetic level. A relation of aging and Ionizing Radiation (IR) could be demonstrated by involvement of similar mechanisms, e.g. free radical reactions, DNA repair, changes of immune function, altered lipid metabolism, nervous system effects, etc.

Concepts of immanent and interactional ambivalence (electron donor-acceptor dichotomy) of free radicals in their reactivity, and of free-radical ambivalence in biochemical processes, can be used to analyze free-radical function in normal and pathologic conditions including aging after IR exposure. Prospective epidemiological studies of atomic bomb survivors revealed IR significantly increased mortality for causes other than cancer. Results do not support claims survivors exposed to low IR doses live longer than comparable unexposed individuals. Whether exposure to low dose IR is a risk factor for accelerated aging and neurodegeneration is still unanswered and the biological mechanisms involved unknown. We propose: 1) exposure to low dose IR is a risk factor for accelerated aging and neurodegeneration; 2) heterogeneous pathogenetic factors contribute to the acceleration. International efforts to organize studies to test these hypotheses are of significance for radiation medicine and gerontology.

URL: http://topreferat.znate.ru/docs/index-1478.html

Differential recovery of neural stem cells in the subventricular zone and dentate gyrus after ionizing radiation

Author: N.A. Hellström, T. Björk-Eriksson, K. Blomgren, H.G. Kuhn

Reference: Stem Cells. ― 2009. ― Vol. 27, № 3. ― P. 634–641.

Keywords: CNS, radiotherapy, hippocampal neurogenesis, SVZ

Abstract: Radiation therapy is a widely used treatment for malignant central nervous system tumors. Mature neurons are terminally differentiated, whereas stem and progenitor cells have a prominent proliferative capacity and are therefore highly vulnerable to irradiation. Our aim was to investigate how cranial radiation in young rats would affect stem/progenitor cells in the two niches of adult neurogenesis, the subventricular zone (SVZ) and the dentate gyrus of the hippocampal formation. Nine weeks after irradiation we found that in irradiated animals, hippocampal neurogenesis was reduced to 5% of control levels. Similarly, the numbers of actively proliferating cells and radial glia-like stem cells (nestin+/glial fibrillary acidic protein [GFAP]+) in the dentate gyrus were reduced to 10% and 15% of control levels, respectively. In the irradiated olfactory bulb, neurogenesis was reduced to 40% of control levels, and the number of actively proliferating cells in the SVZ was reduced to 53% of control levels. However, the number of nestin+/GFAP+ cells in the SVZ was unchanged compared with controls. To evaluate the immediate response to the radiation injury, we quantified the amount of proliferation in the SVZ and dentate gyrus 1 day after irradiation. We found an equal reduction in proliferating cells both in dentate gyrus and SVZ. In summary, we show an initial response to radiation injury that is similar in both brain stem cell niches. However, the long-term effects on stem cells and neurogenesis in these two areas differ significantly: the dentate gyrus is severely affected long-term, whereas the SVZ appears to recover with time.

URL: http://www.ncbi.nlm.nih.gov/pubmed/19056908

Study of lymphocyte activation reactions to neuro-specific antigenes in Сhernobyl clean-up workers against the doses of radiation exposure

Author: V.I. Khomenko

Reference: Український медичний часопис. (Ukirainian Medical magazine), 2008

Keywords: Chernobyl accident, autoimmune reactions, protein S-100, myelin basic protein

Abstract: In Chernobyl clean-up workers with cerebrovascular pathology who were irradiated with a range of doses from 30 to 94 cSv the reliable rise of HLA-DR+ lymphocytes activation under protein S-100 stimulation is revealed in comparison with those irradiated in doses up to 30 cSv. It probably testify to the alteration of the glial structures in the central nervous system (CNS) and blood-brain barrier (BBB), that increases under the higher doses irradiation. Glial and endothelial cells of brain vessels are elements of BBB. Conclusions about a probable increase of permeability of the BBB in Chernobyl clean-up workers with cerebrovascular pathology who were irradiated in a range of doses from 30 to 94 cSv, correspond to the results of other studies that have demonstrated an increase of the cerebrovascular discirculation with development of the white and grey brain matter atrophy with the threshold dose for occurrence of these changes 30 cSv. Delay of the HLA-DR+ lymphocyte activation that we observed below this threshold dose is probably connected with the influence of CD4-8+-Т cells on the lymphocyte activation.

URL: http://www.umj.com.ua/article/2215/stan-aktivacijnix-reakcij-limfocitiv-na-nejrospecifichni-antigeni-v-ulna-na-chaes-zalezhno-vid-doz-oprominennya

Post-radiation encephalopathy: experimental studies and clinical observations

Redactor: A.P. Romodanov

Reference: Київ: УНДІНХ АМН України, 1993

Keywords: brain, Central nervous System


Clinical-neuropsychological characteristics of organic mental disorders in a remote period in patients exposed due to the Chernobyl disaster

Author:K.Yu. Antipchuk

Reference: dissert.cand.med.sci., Kiev, 2005

Keywords: brain, left hemisphere, CNS

Abstract: The results of long-term observations indicate local radiation damage to the central nervous system, namely structures anterior left hemisphere, but there are also studies that advocate the existence of diffuse brain damage. Relative laterality of radiation damage to the brain is the evidence of declining functions of the right hemisphere to the left (relatively).

The article contains a whole range of literature: Surma-aho O. et al., 2001; Von der Weid N. et al., 2001; Precourt S. et al., 2002; Lam L.C., 2003; Vines E.F., 2003, Gamache G.L. et al., 2005, Armstrong C.L. et al., 2000; Surma-aho O. et al., 2001; Von der Weid N. et al., 2001; Lam L.C., 2003; Precourt S. et al., 2002, Loganovsky K.N., Loganovskaya T.K., 2000; Kieffer-Renaux V. et al., 2000; Flor-Henry P., 2001; Loganovsky K.N., Yuryev K.L., 2001, 2004; Surma-aho O. et al., 2001; Von der Weid N. et al., 2001; Precourt S. et al., 2002; Бомко М.О., 2004; Gamache G.L. et al., 2005 etc.