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Age dependency of mGluR5 availability in 5xFAD mice measured by PET

Authors
 Minkyung Lee  ;  Hae-June Lee  ;  Ye Ji Jeong  ;  Se Jong Oh  ;  Kyung Jun Kang  ;  Sang Jin Han  ;  Kyung Rok Nam  ;  Yong Jin Lee  ;  Kyo Chul Lee  ;  Young Hoon Ryu  ;  In Young Hyun  ;  Jae Yong Choi 
Citation
 NEUROBIOLOGY OF AGING, Vol.84 : 208-216, 2019-12 
Journal Title
 NEUROBIOLOGY OF AGING 
ISSN
 0197-4580 
Issue Date
2019-12
MeSH
Animals ; Brain / diagnostic imaging* ; Brain / metabolism* ; Mice, Transgenic ; Positron-Emission Tomography* ; Receptor, Metabotropic Glutamate 5 / metabolism*
Keywords
5xFAD ; Alzheimer's disease ; Beta-amyloid ; MRS ; PET
Abstract
The major pathologies of Alzheimer's disease (AD) are amyloid plaques and hyperphosphorylated tau. The deposition of amyloid plaques leads to synaptic dysfunction, neuronal cell death, and cognitive impairment. Among the neurotransmitters, glutamate is the most abundant in the mammalian brain and plays an important role in synaptic plasticity. With respect to synaptic transmission, metabotropic glutamate receptor 5 (mGluR5) is highly affected by amyloid pathology. However, the neuropathologic changes in the protein expression of mGluR5 in AD remain unclear. Therefore, to elucidate the alteration in mGluR5 expression with the progression of AD, we performed serial behavioral tests, longitudinal imaging studies, and histopathological immunoassay for both 5xFAD (n = 14) mice and age-matched wild-type mice (n = 14). The 5xFAD mice started showing severe hyperactivity and memory impairment from 7 months of age. In addition, mGluR5 positron emission tomography revealed that while the binding values in the wild-type mice were similar over time, those in 5xFAD mice fluctuated from 5 months of age. Furthermore, the 5xFAD mice presented a 35% decrease in the binding values of their cortical and subcortical areas at 9 months of age compared with those at 3 months of age. Magnetic resonance spectroscopy and histopathological studies showed similar changes. In conclusion, mGluR5 availability changes with age, and mGluR5 positron emission tomography could successfully detect this synaptic change in the 5xFAD mice.
Full Text
https://www.sciencedirect.com/science/article/pii/S0197458019302842
DOI
10.1016/j.neurobiolaging.2019.08.006
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Ryu, Young Hoon(유영훈) ORCID logo https://orcid.org/0000-0002-9000-5563
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180631
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