Nanoformulated Bumetanide Ameliorates Social Deficiency in BTBR Mice Model of Autism Spectrum Disorder

被引:4
|
作者
Lv, Hui [1 ,2 ]
Gu, Xiao [3 ]
Shan, Xingyue [4 ]
Zhu, Tailin [1 ,2 ]
Ma, Bingke [4 ]
Zhang, Hao-Tian [5 ,6 ]
Bambini-Junior, Victorio [7 ]
Zhang, Tiantian
Li, Wei-Guang [8 ,9 ]
Gao, Xiaoling [3 ]
Li, Fei [1 ,2 ]
机构
[1] Shanghai Jiao Tong Univ, Dept Dev & Behav Pediat & Child Primary Care, Xinhua Hosp,Sch Med, Brain & Behav Res Unit,Shanghai Inst Pediat Res, Shanghai, Peoples R China
[2] Shanghai Jiao Tong Univ, Xinhua Hosp, Shanghai Key Lab Childrens Environm Hlth, Minist Educ,Sch Med, Shanghai, Peoples R China
[3] Shanghai Jiao Tong Univ, Shanghai Univ Collaborat Innovat Ctr Translat Med, Sch Med, Dept Pharmacol & Chem Biol, Shanghai, Peoples R China
[4] East China Normal Univ, Minist Educ, Sch Life Sci, Shanghai Key Lab Brain Funct Genom, Shanghai, Peoples R China
[5] Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Brain & Behav Res Unit,Shanghai Inst Pediat Res, Shanghai, Peoples R China
[6] Shanghai Jiao Tong Univ, Xinhua Hosp, Shanghai Key Lab Childrens Environm Hlth, Minist Educ MOE,Sch Med, Shanghai, Peoples R China
[7] Univ Lancaster, Fac Hlth & Med, Div Biomed & Life Sci, Lancaster, England
[8] Fudan Univ, State Key Lab Med Neurobiol, Inst Translat Brain Res, Huashan Hosp,Dept Rehabil Med, Shanghai, Peoples R China
[9] Fudan Univ, Ctr Brain Sci, Minist Educ, Shanghai, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷
基金
中国国家自然科学基金;
关键词
autism spectrum disorder; bumetanide; nanoparticle; social behavior; microglia; MICROGLIAL ACTIVATION; MOUSE MODEL; BRAIN; EXCITATION/INHIBITION; NANOPARTICLES; INHIBITION; DELIVERY; CORTEX; NKCC1;
D O I
10.3389/fimmu.2022.870577
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with few medication options. Bumetanide, an FDA-approved diuretic, has been proposed as a viable candidate to treat core symptoms of ASD, however, neither the brain region related to its effect nor the cell-specific mechanism(s) is clear. The availability of nanoparticles provides a viable way to identify pharmacological mechanisms for use in ASD. Here, we found that treatment with bumetanide, in a systemic and medial prefrontal cortex (mPFC) region-specific way, attenuated social deficits in BTBR mice. Furthermore, using poly (ethylene glycol)-poly(l-lactide) (PEG-PLA) nanoparticles [NP(bumetanide)], we showed that the administration of NP(bumetanide) in a mPFC region-specific way also alleviated the social deficits of BTBR mice. Mechanistically, the behavioral effect of NP(bumetanide) was dependent on selective microglia-specific targeting in the mPFC. Pharmacological depletion of microglia significantly reduced the effect of nanoencapsulation and depletion of microglia alone did not improve the social deficits in BTBR mice. These findings suggest the potential therapeutic capabilities of nanotechnology for ASD, as well as the relevant link between bumetanide and immune cells.
引用
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页数:13
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