Acceleration of NLRP3 inflammasome by chronic cerebral hypoperfusion in Alzheimer's disease model mouse

Jingwei Shang, Toru Yamashita, Yun Zhai, Yumiko Nakano, Ryuta Morihara, Xianghong Li, Feng Tian, Xia Liu, Yong Huang, Xiaowen Shi, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

Research output: Contribution to journalArticle

Abstract

Cerebral neuroinflammation defines a novel pathway for progressing Alzheimer's disease (AD) pathology. We investigated immunohistological changes of neuroinflammation with nucleotide-binding domain and leucine-rich repeat (NLR)-protein 3 (NLRP3), activated caspase-1 and interleukin-1 beta (IL-1β) in a novel AD (APP23) mice with chronic cerebral hypoperfusion (CCH) model from 4 months (M) of age, moreover, examined protective effect of galantamine. CCH strongly enhanced NLRP3, activated caspase-1 and IL-1β expressions in hippocampus and thalamus at age 12 M of AD mice. CCH also exaggerated amyloid-beta (Aβ) 40 depositions in cerebral cortex. Furthermore, CCH exacerbated a marked dissociation of neurovascular unit (NVU). These pathological changes were ameliorated by galantamine treatment. The present study demonstrated that CCH strongly enhanced primary AD pathology including neuroinflammation, Aβ accumulations and NVU dissociation in AD mice, which was greatly protected by an allosterically potentiating ligand galantamine.

LanguageEnglish
JournalNeuroscience Research
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Inflammasomes
Galantamine
Alzheimer Disease
Caspase 1
Pathology
Thalamus
Interleukin-1beta
Amyloid
Cerebral Cortex
Hippocampus
Ligands
NLR Proteins

Keywords

  • Alzheimer's disease
  • Chronic cerebral hypoperfusion
  • Galantamine
  • Neuroinflammation
  • Neurovascular unit dissociation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Acceleration of NLRP3 inflammasome by chronic cerebral hypoperfusion in Alzheimer's disease model mouse. / Shang, Jingwei; Yamashita, Toru; Zhai, Yun; Nakano, Yumiko; Morihara, Ryuta; Li, Xianghong; Tian, Feng; Liu, Xia; Huang, Yong; Shi, Xiaowen; Sato, Kota; Takemoto, Mami; Hishikawa, Nozomi; Ohta, Yasuyuki; Abe, Koji.

In: Neuroscience Research, 01.01.2018.

Research output: Contribution to journalArticle

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