BCI-838, an orally active mGluR2/3 receptor antagonist pro-drug, rescues learning behavior deficits in the PS19 MAPTP301S mouse model of tauopathy.
BCI-838, an orally active mGluR2/3 receptor antagonist pro-drug, rescues learning behavior deficits in the PS19 MAPTP301S mouse model of tauopathy.
复制标题
BCI-838 是一种口服活性 mGluR2/3 受体拮抗剂前药，可挽救 PS19 MAPTP301S tau 蛋白病小鼠模型的学习行为缺陷。
DOI：
10.1016/j.neulet.2023.137080
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发表时间：
2023
影响因子：
2.5
通讯作者：
Elder,Gregory
中科院分区：
文献类型：
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作者：
Perez-Garcia,Georgina;Bicak,Mesude;Haure-Mirande,Jean-Vianney;Perez,GisselM;Otero-Pagan,Alena;GamaSosa,MiguelA;DeGasperi,Rita;Sano,Mary;Barlow,Carrolee;Gage,FredH;Readhead,Benjamin;Ehrlich,MichelleE;Gandy,Sam;Elder,Gregory
Tauopathies are a heterogeneous group of neurodegenerative disorders that are clinically and pathologically distinct from Alzheimer’s disease (AD) having tau inclusions in neurons and/or glia as their most prominent neuropathological feature. BCI-838 (MGS00210) is a group II metabotropic glutamate receptor (mGluR2/3) antagonist pro-drug. Previously, we reported that orally administered BCI-838 improved learning behavior and reduced anxiety in Dutch (APPE693Q) transgenic mice, a model of the pathological accumulation of Aβ oligomers found in AD. Herein, we investigated effects of BCI-838 on PS19 male mice that express the tauopathy mutationMAPTP301Sassociated with human frontotemporal lobar degeneration (FTLD). These mice develop an aging-related tauopathy without amyloid accumulation. Mice were divided into three experimental groups: (1) non-transgenic wild type mice treated with vehicle, (2) PS19 mice treated with vehicle and (3) PS19 mice treated with 5 mg/kg BCI-838. Groups of 10–13 mice were utilized. Vehicle or BCI-838 was administered by oral gavage for 4 weeks. Behavioral testing consisting of a novel object recognition task was conducted after drug administration. Two studies were performed beginning treatment of mice at 3 or 7 months of age. One month of BCI-838 treatment rescued deficits in recognition memory in PS19 mice whether treatment was begun at 3 or 7 months of age. These studies extend the potential utility of BCI-838 to neurodegenerative conditions that have tauopathy as their underlying basis. They also suggest an mGluR2/3 dependent mechanism as a basis for the behavioral deficits in PS19 mice.
