Evaluation of oxidative stress in the brain of a transgenic mouse model of Alzheimer disease by in vivo electron paramagnetic resonance imaging

Matsumura, Akihiro; Emoto, Miho C.; Suzuki, Syuuichirou; Iwahara, Naotoshi; Hisahara, Shin; Kawamata, Jun; Suzuki, Hiromi; Yamauchi, Ayano; Sato-Akaba, Hideo; Fujii, Hirotada; Shimohama, Shun

doi:10.1016/j.freeradbiomed.2015.04.013

Cited by 50 publications

(34 citation statements)

References 63 publications

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“…Quest MRI offers advantages compared to other imaging methods that report on oxidative stress in vivo (52,55,57,(75)(76)(77)(78)(79). These other methods involve exogenously administered contrast agents that bind to free radicals (spin traps) and/or require highly specialized equipment (e.g., ref.…”

Section: Discussionmentioning

confidence: 99%

In vivoimaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome

et al. 2017

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Hippocampus oxidative stress is considered pathogenic in neurodegenerative diseases, such as Alzheimer disease (AD), and in neurodevelopmental disorders, such as Angelman syndrome (AS). Yet clinical benefits of antioxidant treatment for these diseases remain unclear because conventional imaging methods are unable to guide management of therapies in specific hippocampus subfields that underlie abnormal behavior. Excessive production of paramagnetic free radicals in nonhippocampus brain tissue can be measured as a greater-than-normal 1/ that is quenchable with antioxidant as measured by quench-assisted (Quest) MRI. Here, we further test this approach in phantoms, and we present proof-of-concept data in models of AD-like and AS hippocampus oxidative stress that also exhibit impaired spatial learning and memory. AD-like models showed an abnormal gradient along the CA1 dorsal-ventral axis of excessive free radical production as measured by Quest MRI, and redox-sensitive calcium dysregulation as measured by manganese-enhanced MRI and electrophysiology. In the AS model, abnormally high free radical levels were observed in dorsal and ventral CA1. Quest MRI is a promising paradigm for bridging brain subfield oxidative stress and behavior in animal models and in human patients to better manage antioxidant therapy in devastating neurodegenerative and neurodevelopmental diseases.-Berkowitz, B. A., Lenning, J., Khetarpal, N., Tran, C., Wu, J. Y., Berri, A. M., Dernay, K., Haacke, E. M., Shafie-Khorassani, F., Podolsky, R. H., Gant, J. C., Maimaiti, S., Thibault, O., Murphy, G. G., Bennett, B. M., Roberts, R. imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome.

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Section: Discussionmentioning

confidence: 99%

In vivoimaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome

et al. 2017

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“…For example, the role of oxidative stress by reactive oxygen species (Van Everbroeck et al, 2004) and microglial toxicity (Brown, 2001; Amor et al, 2010) has been shown in prion diseases, as well as in Alzheimer's disease (Rapic et al, 2013; Heneka et al, 2015; Matsumura et al, 2015), Parkinson's disease (Aras et al, 2014; Borrajo et al, 2014; Kim et al, 2015) and Huntington's disease (Crotti et al, 2014; Rotblat et al, 2014). Specifically, early oxidative stress causing lipid peroxidation is linked to propagation of pathologic prion protein accumulation and to typical neuropathological changes in prion disease (Brazier et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Chronic Progressive Neurodegeneration in a Transgenic Mouse Model of Prion Disease

et al. 2016

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Neurodegenerative diseases present pathologically with progressive structural destruction of neurons and accumulation of mis-folded proteins specific for each condition leading to brain atrophy and functional disability. Many animal models exert deposition of pathogenic proteins without an accompanying neurodegeneration pattern. The lack of a comprehensive model hinders efforts to develop treatment. We performed longitudinal quantification of cellular, neuronal and synaptic density, as well as of neurogenesis in brains of mice mimicking for genetic Creutzfeldt-Jacob disease as compared to age-matched wild-type mice. Mice exhibited a neurodegenerative process of progressive reduction in cortical neurons and synapses starting at age of 4–6 months, in accord with neurologic disability. This was accompanied by significant decrease in subventricular/subependymal zone neurogenesis. Although increased hippocampal neurogenesis was detected in mice, a neurodegenerative process of CA1 and CA3 regions associated with impaired hippocampal-dependent memory function was observed. In conclusion, mice exhibit pathological neurodegeneration concomitant with neurological disease progression, indicating these mice can serve as a model for neurodegenerative diseases.

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“…Uno de los desafíos que afronta la célula constantemente es la acumulación de ROS como consecuencia de exposición a sustancias químicas, radiación, metabolismo y envejecimiento celular. De hecho, cuando aumenta la producción de ROS o los sistemas antioxidantes son ineficientes, se pueden inducir lesiones celulares relacionadas con múltiples procesos patológicos, incluidos el cáncer, el envejecimiento y algunos procesos degenerativos como el Alzheimer (Marteijn et al 2014, Matsumura et al 2015, Muñoz-Espín y Serrano 2014).…”

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Protección celular antioxidante y respuesta adaptativa inducida por estímulos oxidativos crónicos

Santa-González

Camargo

2016

Actual Biol

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ResumenLa adaptación es un importante mecanismo por el cual las células y los organismos responden a retos ambientales y a cambiantes necesidades funcionales. Para lograrlo, las células integran cambios en el fenotipo, actividad metabólica, expresión génica y función celular, que deben coordinarse adecuadamente para mantener la viabilidad ante estímulos nocivos, como es el caso del reto ante un exceso de especies reactivas de oxígeno (ROS). En este estudio, se evaluó la hipótesis que pulsos crónicos y repetitivos con peróxido de hidrógeno (H 2 O 2 ), pueden activar respuestas celulares que resultan en adaptación a estrés oxidativo. Para probar esto, se estableció un modelo in vitro, donde las células de origen mioblastoide C2C12, fueron expuestas a 5 mU/ml de la enzima glucosa oxidasa que durante breves pulsos de 1 hora/día genera una concentración constante de 50 µM de H 2 O 2 en el medio. Este régimen de tratamiento se extendió durante 7 días, tras los cuales se evaluaron los efectos sobre la morfología y viabilidad celular, el contenido de ADN mitocondrial, la acumulación de ROS mitocondrial y la expresión de genes de defensa antioxidante. Los resultados obtenidos apoyan la idea de que los estímulos prolongados, repetitivos y a bajas concentraciones de ROS, pueden actuar como moléculas de señalización induciendo procesos celulares que convergen en la adaptación al estrés oxidativo crónico.Palabras clave: adaptación, defensa antioxidante, estrés oxidativo crónico, homeostasis AbstractAdaptation is an important mechanism in cells and organisms that allow them to respond to environmental challenges and changing functional demands. To accomplish these requirements, cells integrate modifications at different levels such as gene expression, metabolic activity, cellular functionality and phenotype. The orderly coordination of these changes is fundamental for cells to maintain viability despite a variety of harmful stimuli, such as the case of exceedingly concentrations of reactive oxygen species (ROS). In this study, we tested the hypothesis that chronic and repetitive stimuli with a mild concentration of hydrogen peroxide (H 2 O 2 ) would activate cellular responses, resulting in adaptation. This was done confronting cell cultures to prolonged exposures of H 2 O 2 obtained with glucose oxydase (GlucOx) added to the medium to generate a constant concentration of the oxidant (≈ 50 µM); this treatment protocol (1h/d) was extended during seven continuous consecutive days after which the following parameters were evaluated: cell morphology and viability, mitochondrial DNA content, mitochondrial ROS accumulation and antioxidant defense gene expression. These data further support the idea that exposure to continuous and low concentrations of ROS, could act as signaling molecules inducing cellular processes that converged toward adaptation to chronic oxidative stress. El objetivo de este estudio fue evaluar la capacidad de las células musculares para responder al estrés oxidativo inducido por la exposición crónica y repeti...

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Evaluation of oxidative stress in the brain of a transgenic mouse model of Alzheimer disease by in vivo electron paramagnetic resonance imaging

Cited by 50 publications

References 63 publications

In vivoimaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome

In vivoimaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome

Chronic Progressive Neurodegeneration in a Transgenic Mouse Model of Prion Disease

Protección celular antioxidante y respuesta adaptativa inducida por estímulos oxidativos crónicos

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