Yanyan Kong, Lei Cao, Jiao Wang, Junyi Zhuang, Yongshan Liu, Lei Bi, Yifan Qiu, Yuyi Hou, Qi Huang, Fang Xie, Yunhao Yang, Kuangyu Shi, Axel Rominger, Yihui Guan, Hongjun Jin* and Ruiqing Ni*,
{"title":"通过 PET 使用 [18F]GSK1482160 评估 Tauopathy 小鼠模型中 P2X7R 的大脑水平升高。","authors":"Yanyan Kong, Lei Cao, Jiao Wang, Junyi Zhuang, Yongshan Liu, Lei Bi, Yifan Qiu, Yuyi Hou, Qi Huang, Fang Xie, Yunhao Yang, Kuangyu Shi, Axel Rominger, Yihui Guan, Hongjun Jin* and Ruiqing Ni*, ","doi":"10.1021/acschemneuro.4c00067","DOIUrl":null,"url":null,"abstract":"<p >Neuroinflammation plays an important role in Alzheimer’s disease and primary tauopathies. The aim of the current study was to map [<sup>18</sup>F]GSK1482160 for imaging of purinergic P2X7R in Alzheimer’s disease and primary tauopathy mouse models. Small animal PET was performed using [<sup>18</sup>F]GSK1482160 in widely used mouse models of Alzheimer’s disease (APP/PS1, 5×FAD, and 3×Tg), 4-repeat tauopathy (rTg4510) mice, and age-matched wild-type mice. Increased uptake of [<sup>18</sup>F]GSK1482160 was observed in the brains of 7-month-old rTg4510 mice compared to wild-type mice and compared to 3-month-old rTg4510 mice. A positive correlation between hippocampal tau [<sup>18</sup>F]APN-1607 and [<sup>18</sup>F]GSK1482160 uptake was found in rTg4510 mice. No significant differences in the uptake of [<sup>18</sup>F]GSK1482160 was observed for APP/PS1 mice, 5×FAD mice, or 3×Tg mice. Immunofluorescence staining further indicated the distribution of P2X7Rs in the brains of 7-month-old rTg4510 mice with accumulation of tau inclusion. These findings provide in vivo imaging evidence for an increased level of P2X7R in the brains of tauopathy mice.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschemneuro.4c00067","citationCount":"0","resultStr":"{\"title\":\"Increased Cerebral Level of P2X7R in a Tauopathy Mouse Model by PET Using [18F]GSK1482160\",\"authors\":\"Yanyan Kong, Lei Cao, Jiao Wang, Junyi Zhuang, Yongshan Liu, Lei Bi, Yifan Qiu, Yuyi Hou, Qi Huang, Fang Xie, Yunhao Yang, Kuangyu Shi, Axel Rominger, Yihui Guan, Hongjun Jin* and Ruiqing Ni*, \",\"doi\":\"10.1021/acschemneuro.4c00067\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Neuroinflammation plays an important role in Alzheimer’s disease and primary tauopathies. The aim of the current study was to map [<sup>18</sup>F]GSK1482160 for imaging of purinergic P2X7R in Alzheimer’s disease and primary tauopathy mouse models. Small animal PET was performed using [<sup>18</sup>F]GSK1482160 in widely used mouse models of Alzheimer’s disease (APP/PS1, 5×FAD, and 3×Tg), 4-repeat tauopathy (rTg4510) mice, and age-matched wild-type mice. Increased uptake of [<sup>18</sup>F]GSK1482160 was observed in the brains of 7-month-old rTg4510 mice compared to wild-type mice and compared to 3-month-old rTg4510 mice. A positive correlation between hippocampal tau [<sup>18</sup>F]APN-1607 and [<sup>18</sup>F]GSK1482160 uptake was found in rTg4510 mice. No significant differences in the uptake of [<sup>18</sup>F]GSK1482160 was observed for APP/PS1 mice, 5×FAD mice, or 3×Tg mice. Immunofluorescence staining further indicated the distribution of P2X7Rs in the brains of 7-month-old rTg4510 mice with accumulation of tau inclusion. These findings provide in vivo imaging evidence for an increased level of P2X7R in the brains of tauopathy mice.</p>\",\"PeriodicalId\":13,\"journal\":{\"name\":\"ACS Chemical Neuroscience\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-05-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.acs.org/doi/epdf/10.1021/acschemneuro.4c00067\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Chemical Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acschemneuro.4c00067\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Chemical Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acschemneuro.4c00067","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
神经炎症在阿尔茨海默病和原发性陶陶病中发挥着重要作用。本研究旨在绘制[18F]GSK1482160在阿尔茨海默病和原发性tauopathy小鼠模型中的嘌呤能P2X7R成像图。使用[18F]GSK1482160对广泛使用的阿尔茨海默病小鼠模型（APP/PS1、5×FAD和3×Tg）、4-重复tauopathy（rTg4510）小鼠和年龄匹配的野生型小鼠进行了小动物PET成像。与野生型小鼠和3个月大的rTg4510小鼠相比，7个月大的rTg4510小鼠大脑中[18F]GSK1482160的摄取量增加。在rTg4510小鼠中，海马tau[18F]APN-1607和[18F]GSK1482160的摄取量呈正相关。APP/PS1小鼠、5×FAD小鼠或3×Tg小鼠的[18F]GSK1482160摄取量无明显差异。免疫荧光染色进一步表明，P2X7Rs 在 7 个月大的 rTg4510 小鼠大脑中的分布与 tau 包涵体的累积有关。这些发现提供了体内成像证据，证明在tauopathy小鼠大脑中P2X7R水平升高。
Increased Cerebral Level of P2X7R in a Tauopathy Mouse Model by PET Using [18F]GSK1482160
Neuroinflammation plays an important role in Alzheimer’s disease and primary tauopathies. The aim of the current study was to map [18F]GSK1482160 for imaging of purinergic P2X7R in Alzheimer’s disease and primary tauopathy mouse models. Small animal PET was performed using [18F]GSK1482160 in widely used mouse models of Alzheimer’s disease (APP/PS1, 5×FAD, and 3×Tg), 4-repeat tauopathy (rTg4510) mice, and age-matched wild-type mice. Increased uptake of [18F]GSK1482160 was observed in the brains of 7-month-old rTg4510 mice compared to wild-type mice and compared to 3-month-old rTg4510 mice. A positive correlation between hippocampal tau [18F]APN-1607 and [18F]GSK1482160 uptake was found in rTg4510 mice. No significant differences in the uptake of [18F]GSK1482160 was observed for APP/PS1 mice, 5×FAD mice, or 3×Tg mice. Immunofluorescence staining further indicated the distribution of P2X7Rs in the brains of 7-month-old rTg4510 mice with accumulation of tau inclusion. These findings provide in vivo imaging evidence for an increased level of P2X7R in the brains of tauopathy mice.
期刊介绍：
ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following:
Neurotransmitters and receptors
Neuropharmaceuticals and therapeutics
Neural development—Plasticity, and degeneration
Chemical, physical, and computational methods in neuroscience
Neuronal diseases—basis, detection, and treatment
Mechanism of aging, learning, memory and behavior
Pain and sensory processing
Neurotoxins
Neuroscience-inspired bioengineering
Development of methods in chemical neurobiology
Neuroimaging agents and technologies
Animal models for central nervous system diseases
Behavioral research
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
