Constitutive Ras activity induces hippocampal hypertrophy and remodeling of pyramidal neurons in synRas mice
Constitutive Ras activity induces hippocampal hypertrophy and remodeling of pyramidal neurons in synRas mice
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DOI：
10.1002/jnr.20194
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发表时间：
2004-09-01
影响因子：
4.2
通讯作者：
Arendt, T
中科院分区：
文献类型：
--
作者：
Gärtner, U;Alpár, A;Arendt, T
小G蛋白Ras在神经营养信号转导中起重要作用，它与发育和成年神经系统的神经元可塑性有关。在本研究中，累积效应的组成Ras活性从出生后的早期发展到成年后的海马锥体神经元的形态进行了研究，在syn-Ras小鼠过表达Val 12-Ha-Ras有丝分裂后的大鼠突触蛋白I启动子的控制下。在syn-Ras小鼠中，体视学研究显示海马肥大与CA 2/CA 3区域和齿状回内锥体神经元的核周大小增加相关。荧光黄填充的CA 1锥体神经元的形态计量学分析，此外，表现出相当大的扩张的树突状乔木。基底树突大小的增加主要是由于中间和远端节段的改变，并与扩大的树突表面。顶端树突表现出类似的，但更温和的变化，这主要是由于延长的终端段。Sholl分析说明了更高的复杂性的基础和顶端的树木。尽管有显著的形态学改变，树枝状乔木保留其主要的设计原则。CA 1辐射层内的突触密度保持不变，但是，增加总海马体积和顶端树突大小意味着突触接触的绝对数量的增加。这里提出的数据表明，Ras依赖的信号在海马锥体神经元的成熟和维护过程中的形态调节过程中的重要参与。(C)2004 Wiley-Liss，Inc.
The small G protein Ras, which is involved critically in neurotrophic signal transduction, has been implicated in neuronal plasticity of both the developing and the adult nervous systems. In the present study, the cumulative effects of constitutive Ras activity from early in postnatal development into the adult upon the morphology of hippocampal pyramidal neurons were investigated in syn-Ras mice overexpressing Val12-Ha-Ras postmitotically under the control of the rat synapsin I promoter. In syn-Ras mice, stereologic investigations revealed hypertrophy of the hippocampus associated with an increase in perikaryal size of pyramidal neurons within the CA2/CA3 region and the gyrus dentatus. Morphometric analyses of Lucifer Yellow-filled CA1 pyramidal neurons, in addition, demonstrated considerable expansion of dendritic arbors. The increase in basal dendritic size was caused primarily by alterations of intermediate and distal segments and was associated with an enlarged dendritic surface. Apical dendrites showed similar but more moderate changes, which were attributed mainly to elongation of terminal segments. Sholl analyses illustrated higher complexity of both basal and apical trees. Despite significant morphologic alterations, dendritic arbors preserve their major design principles. The synaptic density within the stratum radiatum of CA1 remained unchanged; however, increases in the total hippocampal volume and in apical dendritic size imply an increment in the absolute number of synaptic contacts. The data presented here suggest a critical involvement of Ras dependent signaling in morphoregulatory processes during the maturation and in the maintenance of hippocampal pyramidal neurons. (C) 2004 Wiley-Liss, Inc.