Serotonin 5‐HT7 receptor increases the density of dendritic spines and facilitates synaptogenesis in forebrain neurons
Serotonin 5‐HT7 receptor increases the density of dendritic spines and facilitates synaptogenesis in forebrain neurons
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血清素 5âHT7 受体增加树突棘的密度并促进前脑神经元的突触发生
DOI：
10.1111/jnc.13962
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发表时间：
2017
影响因子：
4.7
通讯作者：
Ponimaskin E
中科院分区：
文献类型：
--
作者：
Speranza L;Labus J;Volpicelli F;Guseva D;Lacivita E;Leopoldo M;Bellenchi G;di Porzio U;Bijata M;Perrone-Capano C;Ponimaskin E
树突棘密度和突触形成的精确控制对于正常和病理性脑功能至关重要。因此，影响树突生长和重塑的信号通路仍然是广泛研究的主题。在这里，我们报告了选择性激动剂LP-211对5-羟色胺5-HT 7受体（5-HT 7 R）的长期激活促进了树突棘的形成，并促进了出生后皮质和纹状体神经元的突触发生。通过分析从5-HT 7 R-缺陷小鼠中分离的神经元和通过受体的药理学失活证实了5-HT 7 R在神经元形态发生中的关键作用。5-HT 7 R的急性激活导致出生后纹状体和皮质神经元中的神经突显著伸长，从而扩展了先前关于5-HT 7 R在胚胎和海马神经元中的形态发生作用的数据。我们还观察到，在遗传（即5-HT 7 R-敲除）或拮抗剂（即拮抗剂治疗）阻断5-HT 7 R的神经元中，棘的数量减少，表明组成性5-HT 7 R活性在棘发生中至关重要。此外，细胞周期蛋白依赖性激酶5和小G蛋白Cdc 42被确定为介导5-HT 7 R在神经元中的形态发生作用的重要下游效应物。总之，我们的数据表明，出生后发育过程中5-HT 7 R介导的结构重组可能对前脑区域（如皮质和纹状体）的发育和可塑性起着至关重要的作用，因此可能与高级认知功能的调节有关。
Precise control of dendritic spine density and synapse formation is critical for normal and pathological brain functions. Therefore, signaling pathways influencing dendrite outgrowth and remodeling remain a subject of extensive investigations. Here, we report that prolonged activation of the serotonin 5‐HT7 receptor (5‐HT7R) with selective agonist LP‐211 promotes formation of dendritic spines and facilitates synaptogenesis in postnatal cortical and striatal neurons. Critical role of 5‐HT7R in neuronal morphogenesis was confirmed by analysis of neurons isolated from 5‐HT7R‐deficient mice and by pharmacological inactivation of the receptor. Acute activation of 5‐HT7R results in pronounced neurite elongation in postnatal striatal and cortical neurons, thus extending previous data on the morphogenic role of 5‐HT7R in embryonic and hippocampal neurons. We also observed decreased number of spines in neurons with either genetically (i.e. 5‐HT7R‐knock‐out) or pharmacologically (i.e. antagonist treatment) blocked 5‐HT7R, suggesting that constitutive 5‐HT7R activity is critically involved in the spinogenesis. Moreover, cyclin‐dependent kinase 5 and small GTPase Cdc42 were identified as important downstream effectors mediating morphogenic effects of 5‐HT7R in neurons. Altogether, our data suggest that the 5‐HT7R‐mediated structural reorganization during the postnatal development might have a crucial role for the development and plasticity of forebrain areas such as cortex and striatum, and thereby can be implicated in regulation of the higher cognitive functions.Read the Editorial Highlight for this article on page 644.
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通过神经递质受体和小 GTP 酶在神经元中发出形态发生信号
影响因子：
5.1
作者：
E. Ponimaskin;T. Voyno;D. Richter;M. Schachner;Alexander E Dityatev
通讯作者：
Alexander E Dityatev
5-羟色胺受体 7 通过 ERK 和 Cdk5 信号通路促进神经突生长
影响因子：
4.7
作者：
Luisa Speranza;Angela Chambery;M. D. Domenico;M. Crispino;Valeria Severino;Floriana Volpicelli;Marcello Leopoldo;G. Bellenchi;U. Porzio;C. Perrone
通讯作者：
C. Perrone
影响因子：
10.6
作者：
Costa, Lara;Spatuzza, Michela;Ciranna, Lucia
通讯作者：
Ciranna, Lucia
影响因子：
4.2
作者：
P. Rojas;D. Neira;M. Muñoz;S. Lavandero;J. Fiedler
通讯作者：
P. Rojas;D. Neira;M. Muñoz;S. Lavandero;J. Fiedler
DOI：
10.1073/pnas.87.8.2896
发表时间：
1990-04-01
影响因子：
11.1
作者：
COTECCHIA, S;EXUM, S;LEFKOWITZ, RJ
通讯作者：
LEFKOWITZ, RJ