TY - JOUR
T1 - Acceleration of NLRP3 inflammasome by chronic cerebral hypoperfusion in Alzheimer's disease model mouse
AU - Shang, Jingwei
AU - Yamashita, Toru
AU - Zhai, Yun
AU - Nakano, Yumiko
AU - Morihara, Ryuta
AU - Li, Xianghong
AU - Tian, Feng
AU - Liu, Xia
AU - Huang, Yong
AU - Shi, Xiaowen
AU - Sato, Kota
AU - Takemoto, Mami
AU - Hishikawa, Nozomi
AU - Ohta, Yasuyuki
AU - Abe, Koji
N1 - Funding Information:
This work was supported by Hirose International Scholarship Foundation .
Publisher Copyright:
© 2018 Elsevier B.V. and Japan Neuroscience Society
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Chronic cerebral hypoperfusion
KW - Galantamine
KW - Neuroinflammation
KW - Neurovascular unit dissociation
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U2 - 10.1016/j.neures.2018.06.002
DO - 10.1016/j.neures.2018.06.002
M3 - Article
C2 - 29885344
AN - SCOPUS:85048281120
SN - 0168-0102
VL - 143
SP - 61
EP - 70
JO - Neuroscience Research
JF - Neuroscience Research
ER -