Dicer expression is essential for adult midbrain dopaminergic neuron maintenance and survival.
Dicer expression is essential for adult midbrain dopaminergic neuron maintenance and survival.
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DICER表达对于成年中脑多巴胺能神经元维持和生存至关重要。
DOI：
10.1016/j.mcn.2013.10.009
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Tapper AR
中科院分区：
文献类型：
--
作者：
Pang X;Hogan EM;Casserly A;Gao G;Gardner PD;Tapper AR
III型RNA酶Dicer负责将microRNA（miRNA）前体加工成功能性miRNA分子，即结合并靶向信使RNA进行抑制的非编码RNA。Dicer表达对于小鼠出生后早期中脑发育和多巴胺能（DA能）神经元的维持和存活是必不可少的。然而，Dicer在成年小鼠DA能神经元维持和存活中的作用尚不清楚。为了弥合这一知识差距，我们在成年floxed Dicer敲入小鼠（Dicerflox/flox）中通过病毒介导的Cre表达，选择性地敲低Dicer在单个DA能中脑区域（包括腹侧被盖区（VTA）和黑质背侧部（SNpc））中的表达。双侧腹侧被盖区Dicer缺失导致进行性活动过度，多巴胺激动剂安非他明可显著降低进行性活动过度。与此相反，在SNpc的Dicer表达下降并不影响运动活动，但诱导运动学习障碍的加速旋转。在成年Dicerflox/flox小鼠的两个中脑区域中敲低Dicer导致DA能神经元的优先进行性损失，这可能解释了运动行为表型。此外，在中脑区域敲低Dicer通过细胞凋亡引发神经元死亡。总之，这些数据表明，Dicer表达，因此，miRNA功能，是必不可少的DA能神经元的维持和存活在成年中脑DA能神经元脑区。
The type III RNAse, Dicer, is responsible for the processing of microRNA (miRNA) precursors into functional miRNA molecules, non-coding RNAs that bind to and target messenger RNAs for repression. Dicer expression is essential for mouse midbrain development and dopaminergic (DAergic) neuron maintenance and survival during the early post-natal period. However, the role of Dicer in adult mouse DAergic neuron maintenance and survival is unknown. To bridge this gap in knowledge, we selectively knocked-down Dicer expression in individual DAergic midbrain areas, including the ventral tegmental area (VTA) and substantia nigra pars compacta (SNpc) via viral-mediated expression of Cre in adult floxed Dicer knock-in mice (Dicerflox/flox). Bilateral Dicer loss in the VTA resulted in progressive hyperactivity that was significantly reduced by the dopamine agonist, amphetamine. In contrast, decreased Dicer expression in the SNpc did not affect locomotor activity but did induce motor-learning impairment on an accelerating rotarod. Knock-down of Dicer in both midbrain regions of adult Dicerflox/flox mice resulted in preferential, progressive loss of DAergic neurons likely explaining motor behavior phenotypes. In addition, knock-down of Dicer in midbrain areas triggered neuronal death via apoptosis. Together, these data indicate that Dicer expression and, as a consequence, miRNA function, is essential for DAergic neuronal maintenance and survival in adult midbrain DAergic neuron brain areas.
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影响因子：
11.2
作者：
Beeler, Jeff A.;Cao, Zhen Fang Huang;Kheirbek, Mazen A.;Ding, Yunmin;Koranda, Jessica;Murakami, Mari;Kang, Un Jung;Zhuang, Xiaoxi
通讯作者：
Zhuang, Xiaoxi
影响因子：
16.2
作者：
Pietrzykowski AZ;Friesen RM;Martin GE;Puig SI;Nowak CL;Wynne PM;Siegelmann HT;Treistman SN
通讯作者：
Treistman SN
影响因子：
56.9
作者：
Kim, Jongpil;Inoue, Keiichi;Abeliovich, Asa
通讯作者：
Abeliovich, Asa
影响因子：
2.7
作者：
Chagniel, Laure;Robitaille, Christine;Cyr, Michel
通讯作者：
Cyr, Michel
影响因子：
5.3
作者：
Davis, Tigwa H.;Cuellar, Trinna L.;Ullian, Erik M.
通讯作者：
Ullian, Erik M.