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Orexin A peptidergic system: comparative sleep behavior, morphology and population in brains between wild type and Alzheimer's disease mice.

Abstract
Sleep disturbance is common in patients with Alzheimer's disease (AD), and orexin A is a pivotal neurotransmitter for bidirectionally regulating the amyloid-β (Aβ) deposition of AD brain and poor sleep. In the present study, we examined the characteristic of sleep-wake architecture in APPswe/PSldE9 (APP/PS1) and Aβ-treated mice using electroencephalogram (EEG) and electromyographic (EMG) analysis. We compared the expression of orexin A, distribution, and morphology of the corresponding orexin A-positive neurons using innovative methods including three-dimensional reconstruction and brain tissue clearing between wild type (WT) and APP/PS1 mice. Results from our study demonstrated that increased wakefulness and reduced NREM sleep were seen in APP/PS1 and Aβ treated mice, while the expression of orexin A was significantly upregulated. Higher density and distribution of orexin A-positive neurons were seen in APP/PS1 mice, with a location of 1.06 mm-2.30 mm away from the anterior fontanelle compared to 1.34 mm-2.18 mm away from the anterior fontanelle in WT mice. These results suggested that the population and distribution of orexin A may play an important role in the progression of AD.
AuthorsPeng Zhao, Yaqian You, Zhe Wang, Yanjun Zhou, Gaoshang Chai, Gen Yan, Zhewu Jin, Qing Wang, Hongxu Sun
JournalBrain structure & function (Brain Struct Funct) Vol. 227 Issue 3 Pg. 1051-1065 (Apr 2022) ISSN: 1863-2661 [Electronic] Germany
PMID35066609 (Publication Type: Journal Article)
Copyright© 2022. The Author(s).
Chemical References
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Hcrt protein, mouse
  • Orexins
  • Presenilin-1
Topics
  • Alzheimer Disease (metabolism)
  • Amyloid beta-Peptides (metabolism)
  • Amyloid beta-Protein Precursor (genetics, metabolism)
  • Animals
  • Brain (metabolism)
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Transgenic
  • Orexins (metabolism)
  • Presenilin-1 (genetics, metabolism)
  • Sleep

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