scholarly journals Monte Carlo track structure simulation in studies of biological effects induced by accelerated charged particles in the central nervous system

2019 ◽  
Vol 204 ◽  
pp. 04008 ◽  
Author(s):  
Munkhbaatar Batmunkh ◽  
Lkhagvaa Bayarchimeg ◽  
Aleksandr N. Bugay ◽  
Oidov Lkhagva

Simulating the biological damage induced by charged particles trajectories (tracks) in the central nervous system (CNS) at different levels of its organization (molecular, cellular, and tissue) is a challenge of modern radiobiology studies. According to the recent experimental studies at particle accelerators, the most radiation-sensitive area of the CNS is the hippocampus. In this regards, the development of measurement-based Monte Carlo simulation of radiation-induced alterations in the hippocampus is of great interest to understand the radiobiological effects on the CNS. The present work investigates the influence of charged particles on the hippocampal cells of the rat brain using the Geant4 Monte Carlo radiation transport code. The applied computer simulation provides a method to simulate physics processes and chemical reactions in the developed model of the rat hippocampus, which contains different types of neural cells - pyramidal cells, mature and immature granular cells, mossy cells, and neural stem cells. The distribution of stochastic energy depositions has been obtained and analyzed in critical structures of the hippocampal neurons after irradiation with 600 MeV/u iron particles. The computed energy deposition in irradiated hippocampal neurons following a track of iron ion suggests that most of the energy is accumulated by granular cells. The obtained quantities at the level of molecular targets also assume that NMDA and GABA receptors belong to the most probable targets in the irradiated neural cells.

2010 ◽  
Vol 79 (3) ◽  
pp. 1363-1373 ◽  
Author(s):  
Jianchun Xiao ◽  
Lorraine Jones-Brando ◽  
C. Conover Talbot ◽  
Robert H. Yolken

ABSTRACTStrain type is one of the key factors suspected to play a role in determining the outcome ofToxoplasmainfection. In this study, we examined the transcriptional profile of human neuroepithelioma cells in response to representative strains ofToxoplasmaby using microarray analysis to characterize the strain-specific host cell response. The study of neural cells is of interest in light of the ability ofToxoplasmato infect the brain and to establish persistent infection within the central nervous system. We found that the extents of the expression changes varied considerably among the three strains. Neuroepithelial cells infected withToxoplasmatype I exhibited the highest level of differential gene expression, whereas type II-infected cells had a substantially smaller number of genes which were differentially expressed. Cells infected with type III exhibited intermediate effects on gene expression. The three strains also differed in the individual genes and gene pathways which were altered following cellular infection. For example, gene ontology (GO) analysis indicated that type I infection largely affects genes related to the central nervous system, while type III infection largely alters genes which affect nucleotide metabolism; type II infection does not alter the expression of a clearly defined set of genes. Moreover, Ingenuity Pathways Analysis (IPA) suggests that the three lineages differ in the ability to manipulate their host; e.g., they employ different strategies to avoid, deflect, or subvert host defense mechanisms. These observed differences may explain some of the variation in the neurobiological effects of different strains ofToxoplasmaon infected individuals.


2002 ◽  
Vol 29 (3) ◽  
pp. 319-325 ◽  
Author(s):  
SM MacKenzie ◽  
M Lai ◽  
CJ Clark ◽  
R Fraser ◽  
CE Gomez-Sanchez ◽  
...  

The central nervous system produces many of the enzymes responsible for corticosteroid synthesis. A model system to study the regulation of this local system would be valuable. Previously, we have shown that primary cultures of hippocampal neurons isolated from the fetal rat can perform the biochemical reactions associated with the enzymes 11beta-hydroxylase and aldosterone synthase. Here, we demonstrate directly that these enzymes are present within primary cultures of fetal rat hippocampal neurons.


2001 ◽  
Vol 81 (2) ◽  
pp. 871-927 ◽  
Author(s):  
Nicole Baumann ◽  
Danielle Pham-Dinh

Oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), and astrocytes constitute macroglia. This review deals with the recent progress related to the origin and differentiation of the oligodendrocytes, their relationships to other neural cells, and functional neuroglial interactions under physiological conditions and in demyelinating diseases. One of the problems in studies of the CNS is to find components, i.e., markers, for the identification of the different cells, in intact tissues or cultures. In recent years, specific biochemical, immunological, and molecular markers have been identified. Many components specific to differentiating oligodendrocytes and to myelin are now available to aid their study. Transgenic mice and spontaneous mutants have led to a better understanding of the targets of specific dys- or demyelinating diseases. The best examples are the studies concerning the effects of the mutations affecting the most abundant protein in the central nervous myelin, the proteolipid protein, which lead to dysmyelinating diseases in animals and human (jimpy mutation and Pelizaeus-Merzbacher disease or spastic paraplegia, respectively). Oligodendrocytes, as astrocytes, are able to respond to changes in the cellular and extracellular environment, possibly in relation to a glial network. There is also a remarkable plasticity of the oligodendrocyte lineage, even in the adult with a certain potentiality for myelin repair after experimental demyelination or human diseases.


2018 ◽  
Vol 98 (1) ◽  
pp. 239-389 ◽  
Author(s):  
Alexei Verkhratsky ◽  
Maiken Nedergaard

Astrocytes are neural cells of ectodermal, neuroepithelial origin that provide for homeostasis and defense of the central nervous system (CNS). Astrocytes are highly heterogeneous in morphological appearance; they express a multitude of receptors, channels, and membrane transporters. This complement underlies their remarkable adaptive plasticity that defines the functional maintenance of the CNS in development and aging. Astrocytes are tightly integrated into neural networks and act within the context of neural tissue; astrocytes control homeostasis of the CNS at all levels of organization from molecular to the whole organ.


2016 ◽  
Vol 74 (8) ◽  
pp. 671-678 ◽  
Author(s):  
Roberto E. Sica ◽  
Roberto Caccuri ◽  
Cecilia Quarracino ◽  
Francisco Capani

ABSTRACT Experimental evidence suggests that astrocytes play a crucial role in the physiology of the central nervous system (CNS) by modulating synaptic activity and plasticity. Based on what is currently known we postulate that astrocytes are fundamental, along with neurons, for the information processing that takes place within the CNS. On the other hand, experimental findings and human observations signal that some of the primary degenerative diseases of the CNS, like frontotemporal dementia, Parkinson’s disease, Alzheimer’s dementia, Huntington’s dementia, primary cerebellar ataxias and amyotrophic lateral sclerosis, all of which affect the human species exclusively, may be due to astroglial dysfunction. This hypothesis is supported by observations that demonstrated that the killing of neurons by non-neural cells plays a major role in the pathogenesis of those diseases, at both their onset and their progression. Furthermore, recent findings suggest that astrocytes might be involved in the pathogenesis of some psychiatric disorders as well.


Author(s):  
Andreia Fuentes Santos ◽  
◽  
Marilia Moraes Queiroz Souza ◽  
Karoline Bach Pauli ◽  
Gustavo Ratti da Silva ◽  
...  

Bacopa monnieri(L.) Wettst. (Plantaginaceae), also known as Brahmi, has been used to improve cognitive processes and intellectual functions that are related to the preservation of memory. The objective of this research is to review the ethnobotanical applications, phytochemical composition, toxicity and activity of B. monnieriin the central nervous system. It reviewed articles on B. monnieriusing Google Scholar, SciELO, Science Direct, Lilacs, Medline, and PubMed. Saponins are the main compounds in extracts of B. monnieri. Pharmacological studies showed that B. monnieriimproves learning and memory and presents biological effects against Alzheimer’s disease, Parkinson’s disease, epilepsy, and schizophrenia. No preclinical acute toxicity was reported. However, gastrointestinal side effects were reported in some healthy elderly individuals. Most studies with B. monnierihave been preclinical evaluations of cellular mechanisms in the central nervous system and further translational clinical research needs to be performed to evaluate the safety and efficacy of the plant.


Author(s):  
К. Ляхова ◽  
K. Lyakhova ◽  
И. Колесникова ◽  
I. Kolesnikova ◽  
Д. Утина ◽  
...  

Purpose: Investigation of the dose–time–effect dependency of the behavior of mice and rats after irradiation with accelerated protons and comparison of these data with the morphological changes in the hippocampus and the cerebellum of rodents. Material and methods: Experiments were performed on outbred adult female ICR mice (CD-1), SPF categories, body weight 30–35 g, of the age of 10 weeks – total number 61 animals, and on 39 male Sprague Dawley outbred rats weighing 190–230 g, aged 6.5–7.5 weeks. The animals were irradiated with accelerated protons with energy of 70 MeV on the medical beam of the phasotron of the Joint Institute for Nuclear Research (Dubna). Mice were placed in individual containers and irradiated 4 ones at a time. Irradiation was performed in a modified Bragg peak at doses of 0.5; 1; 2.5 and 5 Gy in caudocranial and craniocaudal direction. Rats were divided into 2 groups: intact control and group irradiated with 170 MeV protons at a dose of 1 Gy, dose rate of 1 Gy / min in the craniocaudal direction. The behavioral responses of experimental animals were tested in the Open Field test on days 1, 7, 14, 30, 90 in rats and on days 8, 30, and 90 in mice. Quantitative analysis of the dilution of Purkinje cells in the rat cerebellum was made, as well as morphological changes in the rat hippocampal neurons. It was shown a development of structural changes after irradiation with protons in neurons of different severity at different times after exposure: after 30 and 90 days. Results: In the period of 1–8 days after proton irradiation of mice and rats in non-lethal doses (0.5–5.0 Gy), there is a dose-independent decrease in the main indicators of the spontaneous locomotor activity of rodents. By the 90th day after irradiation, there is a clear tendency to normalize the indicators of OIR in all groups of irradiated animals, while the ES remains elevated. Disruption of motor activity of rodents irradiated with protons in the early period and its relative normalization in the late post-irradiation period occur on the background of an increased number of morphologically altered and dystrophic neurons in the hippocampus and rarefied of Purkinje cells in the cerebellum. Conclusion: The complex hierarchical structure of the central nervous system, the dependence of its function on the state of the whole organism and its hormonal background, as well as on the state of the blood supply and other factors, along with its high plasticity, require complex physiological, morphological and neurochemical approaches in analyzing the radiobiological effect of corpuscular radiation, taking into consideration the unevenness in dose distribution during irradiation.


1999 ◽  
Vol 5 (S2) ◽  
pp. 1228-1229
Author(s):  
Christopher S. Wallace ◽  
Michael A. Silverman ◽  
Michelle A. Burack ◽  
Janis E. Lochner ◽  
Richard G. Allen ◽  
...  

Recent technical advances in the ability to attach an endogenously fluorescent protein sequence—i.e., green fluorescent protein or GFP and its derivatives--to any protein of experimental interest promises to mark a new era of progress in the study of protein targeting. Bringing these new tools to bear on neurons of the central nervous system has been challenging, however, because they have a very complex structure and are relatively difficult to transfect because they are post-mitotic.We use two cell culture approaches to characterize protein trafficking within neurons of the central nervous system in vitro. The first is a dissociated culture of hippocampal neurons from embryonic (El8) rats which is especially suited to analysis by conventional light microscopy because these neurons are grown on glass coverslips at low density. Neurons cultured in this way develop a morphology comparable to that seen in vivo and permit the establishment of axons and dendrites to be analyzed by time-lapse microscopy.


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