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Suvorexant ameliorates cognitive impairments and pathology in APP/PS1 transgenic mice
- Source :
- Neurobiology of Aging. 91:66-75
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Cognitive impairments and circadian rhythm disorders are the main clinical manifestations of Alzheimer’s disease (AD). Orexin has been reported as abnormally elevated in the cerebrospinal fluid of AD patients, accompanied with cognitive impairments. Our recent research revealed that suvorexant, a dual orexin receptor antagonist, could improve behavioral circadian rhythm disorders in 9-month-old APP/PS1 mice. Here we further observed whether suvorexant could ameliorate the cognitive decline in APP/PS1 mice by using behavioral tests, and investigated the possible mechanisms by in vivo electrophysiological recording, western blot, and immunochemistry. The results showed that suvorexant treatment effectively ameliorated the cognitive impairments, alleviated in vivo hippocampal long-term potentiation suppression, restored the circadian phosphorylated CREB expression in the hippocampus, and reduced amyloid-β protein deposition in the hippocampus and cortex in APP/PS1 mice. These results indicate that the neuroprotective effects of suvorexant against AD are involved in the reduction of amyloid-β plaques, improvement of synaptic plasticity, and circadian expression of phosphorylated CREB, suggesting that suvorexant could be beneficial to the prevention and treatment of AD.
- Subjects :
- 0301 basic medicine
Aging
Long-Term Potentiation
Gene Expression
Hippocampus
Mice, Transgenic
Chronobiology Disorders
CREB
03 medical and health sciences
0302 clinical medicine
Alzheimer Disease
mental disorders
Animals
Neuroprostanes
Medicine
Cognitive Dysfunction
Circadian rhythm
Cognitive decline
Cyclic AMP Response Element-Binding Protein
Orexins
Amyloid beta-Peptides
Neuronal Plasticity
biology
business.industry
General Neuroscience
Suvorexant
Long-term potentiation
Azepines
Triazoles
Orexin receptor
Orexin
Disease Models, Animal
030104 developmental biology
biology.protein
Orexin Receptor Antagonists
Neurology (clinical)
Geriatrics and Gerontology
business
Neuroscience
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 01974580
- Volume :
- 91
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Aging
- Accession number :
- edsair.doi.dedup.....9d6e7040f3362439af62b96660694b31