Chronic intermittent hypoxia induces robust astrogliosis in an Alzheimer’s disease-relevant mouse model
| Autor: | Kyle Ritter, Adam D. Bachstetter, Danielle N. Lyons, Warren J. Alilain, Emma K. Higgins, Teresa Macheda, Ai-Ling Lin, Kelly N. Roberts |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Mice Transgenic Plaque Amyloid Neuropathology Disease Article 03 medical and health sciences Random Allocation 0302 clinical medicine Sleep Apnea Syndromes Alzheimer Disease Internal medicine mental disorders medicine Dementia Animals Gliosis Hypoxia Neuroinflammation business.industry General Neuroscience Sleep apnea Brain medicine.disease Astrogliosis Obstructive sleep apnea Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology Gene Expression Regulation Astrocytes Female business 030217 neurology & neurosurgery Astrocyte |
| Popis: | Sleep disturbances are a common early symptom of neurodegenerative diseases, including Alzheimer’s disease (AD) and other age-related dementias, and emerging evidence suggests that poor sleep may be an important contributor to development of amyloid pathology. Of the causes of sleep disturbances, it is estimated that 10% - 20% of adults in the United States have sleep-disordered breathing (SDB) disorder, with obstructive sleep apnea accounting for the majority of the SBD cases. The clinical and epidemiological data clearly support a link between sleep apnea and AD; yet, almost no experimental research is available exploring the mechanisms associated with this correlative link. Therefore, we exposed an AD-relevant mouse model (APP/PS1 KI) to chronic intermittent hypoxia (an experimental model of sleep apnea) to begin to describe one of the potential mechanisms by which SDB could increase the risk of dementia. Previous studies have found that astrogliosis is a contributor to neuropathology in models of chronic intermittent hypoxia (IH) and AD; therefore, we hypothesized that a reactive astrocyte response might be a contributing mechanism in the neuroinflammation associated with sleep apnea. To test this hypothesis, 10-11-month-old wild type (WT) and APP/PS1 KI mice were exposed to 10 hours of IH, daily for four weeks. At the end of four weeks brains were analyzed from amyloid burden and astrogliosis. No effect was found for chronic IH exposure on amyloid-beta levels or plaque load in the APP/PS1 KI mice. A significant increase in GFAP staining was found in the APP/PS1 KI mice following chronic IH exposure, but not in the WT mice. Profiling of genes associated with different phenotypes of astrocyte activation identified GFAP, CXCL10, and Ggta1 as significant responses activated in the APP/PS1 KI mice exposed to chronic IH. |
| Databáze: | OpenAIRE |
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