Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice

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	Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice
	Li, Xiaoguang 1,2; Wang, Zhihao 1,2; Tan, Lu 3; Wang, Yali 1,2,4; Lu, Chengbiao 4; Chen, Rongxiang 5; Zhang, Shujuan 1,2; Gao, Yuan 1,2; Liu, Yanchao 1,2; Yin, Yaling 1,2
刊名	MOLECULAR THERAPY
	2017-01-04
卷号	25 期号:1 页码:140-152
英文摘要	Patients with Alzheimer's disease (AD) commonly show anxiety behaviors, but the molecular mechanisms are not clear and no efficient intervention exists. Here, we found that overexpression of human wild-type, full-length tau (termed htau) in hippocampus significantly decreased the extracellular gamma-aminobutyric acid (GABA) level with inhibition of gamma oscillation and the evoked inhibitory postsynaptic potential (eIPSP). With tau accumulation, the mice show age-dependent anxiety behaviors. Among the factors responsible for GABA synthesis, release, uptake, and transport, we found that accumulation of htau selectively suppressed expression of the intracellular vesicular GABA transporter (vGAT). Tau accumulation increased miR92a, which targeted vGAT mRNA 3' UTR and inhibited vGAT translation. Importantly, we found that upregulating GABA tones by intraperitoneal injection of midazolam (a GABA agonist), ChR2-mediated photostimulating and over expressing vGAT, or blocking miR92a by using specific antagomir or inhibitor efficiently rescued the htau-induced GABAergic dysfunctions with attenuation of anxiety. Finally, we also demonstrated that vGAT level decreased while the miR92a increased in the AD brains. These findings demonstrate that the AD-like tau accumulation induces anxiety through disrupting miR92a-vGAT-GABA signaling, which reveals molecular mechanisms underlying the anxiety behavior in AD patients and potentially leads to the development of new therapeutics for tauopathies.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
研究领域[WOS]	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
关键词[WOS]	NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; AMYLOID PRECURSOR PROTEIN ; ALZHEIMERS-DISEASE ; TRANSGENIC MICE ; NEUROFIBRILLARY PATHOLOGY ; NETWORK OSCILLATIONS ; MOTOR COORDINATION ; SYNAPTIC VESICLES ; MEMORY DEFICIT ; AMINO-ACIDS
收录类别	SCI
语种	英语
WOS记录号	WOS:000391901600016
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/9962]
专题	武汉物理与数学研究所_磁共振应用研究部
作者单位	1.Huazhong Univ Sci & Technol, Sch Basic Med, Dept Pathophysiol, Tongji Med Coll, Wuhan 430030, Peoples R China 2.Huazhong Univ Sci & Technol, Collaborat Innovat Ctr Brain Sci, Tongji Med Coll, Key Lab,Minist Educ China Neurol Disorders, Wuhan 430030, Peoples R China 3.Huazhong Univ Sci & Technol, Key Lab Mol Diag Hubei Prov, Cent Hosp Wuhan, Tongji Med Coll, Wuhan 430014, Peoples R China 4.Xinxiang Med Univ, Dept Physiol, Henan Prov Key Lab Brain Res, Xinxiang 453000, Peoples R China 5.Chinese Acad Sci, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan Inst Phys & Math, Wuhan 430071, Peoples R China 6.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226001, Peoples R China
推荐引用方式 GB/T 7714	Li, Xiaoguang,Wang, Zhihao,Tan, Lu,et al. Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice[J]. MOLECULAR THERAPY,2017,25(1):140-152.
APA	Li, Xiaoguang.,Wang, Zhihao.,Tan, Lu.,Wang, Yali.,Lu, Chengbiao.,...&Wang, Jian-Zhi.(2017).Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice.MOLECULAR THERAPY,25(1),140-152.
MLA	Li, Xiaoguang,et al."Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice".MOLECULAR THERAPY 25.1(2017):140-152.