In vivoimaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome
| Autor: | Ali M Berri, Geoffrey G. Murphy, Shaniya Maimaiti, Catherine Tran, Robert H. Podolsky, Nikita Khetarpal, Fatema Shafie-Khorassani, Bruce A. Berkowitz, Kristin Dernay, Johnny Y. Wu, John C. Gant, Brian M. Bennett, Olivier Thibault, Jacob Lenning, E. Mark Haacke, Robin Roberts |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Hippocampus medicine.disease_cause Biochemistry 03 medical and health sciences 0302 clinical medicine In vivo Angelman syndrome Genetics medicine Psychiatry Molecular Biology chemistry.chemical_classification Reactive oxygen species business.industry Research medicine.disease 030104 developmental biology chemistry Alzheimer's disease Abnormality business Neuroscience 030217 neurology & neurosurgery Oxidative stress Preclinical imaging Biotechnology |
| Zdroj: | The FASEB Journal. 31:4179-4186 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201700229r |
| Popis: | 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 in vivo that underlie abnormal behavior. Excessive production of paramagnetic free radicals in nonhippocampus brain tissue can be measured in vivo as a greater-than-normal 1/T1 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 in vivo 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. In vivo imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome. |
| Databáze: | OpenAIRE |
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