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

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.

• Authors: 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
• Journal: Neuroscience research (Neurosci Res) Vol. 143 Pg. 61-70 (Jun 2019) ISSN: 1872-8111 [Electronic] Ireland
• PMID: 29885344 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Inflammasomes
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein
• Neuroprotective Agents
• Nlrp3 protein, mouse
• Galantamine
• Collagen
• Casp1 protein, mouse
• Caspase 1

Topics

• Alzheimer Disease (metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Animals
• Brain Ischemia (metabolism, pathology)
• Caspase 1 (metabolism)
• Cerebral Cortex (metabolism, pathology)
• Cerebrovascular Circulation (physiology)
• Collagen (metabolism)
• Disease Models, Animal
• Galantamine (pharmacology)
• Inflammasomes (metabolism)
• Interleukin-1beta (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Neurons (drug effects, pathology)
• Neuroprotective Agents (pharmacology)