Pet-1 is required across different stages of life to regulate serotonergic function.
Pet-1 is required across different stages of life to regulate serotonergic function.
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Pet-1 在生命的不同阶段都需要来调节血清素能功能。
DOI：
10.1038/nn.2623
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发表时间：
2010-10
影响因子：
25
通讯作者：
Deneris, Evan S.
中科院分区：
文献类型：
--
作者：
Liu, Chen;Maejima, Takashi;Wyler, Steven C.;Casadesus, Gemma;Herlitze, Stefan;Deneris, Evan S.
转录级联是5-羟色胺神经元和5-羟色胺调节行为规范所必需的。几个级联因子的表达贯穿整个生命周期，这表明它们对行为的控制可能不会暂时局限于编程正常数量的5-HT神经元。我们应用新的小鼠条件靶向方法来研究对Pet-1的持续需求，Pet-1是启动5-HT合成所需的级联因子，但其表达持续到成年。我们发现，在5-HT神经元生成后，5-HT神经元成熟的多个步骤（包括向体感觉皮层的轴突神经支配、放电特性以及5-HT1A和5-HT1B自身受体的表达）都需要Pet-1。在成人5-HT神经元中靶向Pet-1表明，仍然需要通过直接自动调节5-羟色胺能基因表达来维持正常的焦虑相关行为。这些发现表明，Pet-1在整个生命周期中都是必需的，因此行为发病机制可能是由发育和成年时血清素能转录的改变引起的。
Transcriptional cascades are required for specification of 5-HT neurons and 5-HT modulated behaviors. Expression of several cascade factors extends across lifespan suggesting their control of behavior may not be temporally restricted to programming normal numbers of 5-HT neurons. We applied new mouse conditional targeting approaches to investigate ongoing requirements for Pet-1, a cascade factor required for the initiation of 5-HT synthesis but whose expression persists into adulthood. We found that Pet-1 was required after 5-HT neuron generation, for multiple steps in 5-HT neuron maturation including axonal innervation to the somatosensory cortex, firing properties, and 5-HT1A and 5-HT1B autoreceptor expression. Targeting Pet-1 in adult 5-HT neurons showed that it was still needed to preserve normal anxiety-related behaviors through direct autoregulated control of serotonergic gene expression. These findings show that Pet-1 is required across lifespan and therefore behavioral pathogenesis can result from both developmental and adult-onset alterations in serotonergic transcription.
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DOI：
10.1006/bbrc.1997.7124
发表时间：
1997-08-28
影响因子：
3.1
作者：
Feil, R;Wagner, J;Chambon, P
通讯作者：
Chambon, P
影响因子：
3.3
作者：
Bonnin, A.;Peng, W.;Levitt, P.
通讯作者：
Levitt, P.
影响因子：
4.6
作者：
Craven, SE;Lim, KC;Rosenthal, A
通讯作者：
Rosenthal, A
中枢血清素缺乏小鼠的情境恐惧记忆增强
DOI：
10.1073/pnas.0801329105
发表时间：
2008-08-19
影响因子：
11.1
作者：
Dai, Jin-Xia;Han, Hui-Li;Xu, Lin
通讯作者：
Xu, Lin
影响因子：
8.2
作者：
Holmes, Andrew
通讯作者：
Holmes, Andrew