New model of action for mood stabilizers: phosphoproteome from rat pre-frontal cortex synaptoneurosomal preparations.
New model of action for mood stabilizers: phosphoproteome from rat pre-frontal cortex synaptoneurosomal preparations.
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DOI：
10.1371/journal.pone.0052147
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Richelson E
中科院分区：
文献类型：
--
作者：
Corena-McLeod M;Walss-Bass C;Oliveros A;Gordillo Villegas A;Ceballos C;Charlesworth CM;Madden B;Linser PJ;Van Ekeris L;Smith K;Richelson E
线粒体的短距离和长距离运动对于产生突触信号和可塑性所需的能量是必要的。因此，在神经元放电中，将线粒体运输和锚到突触前和突触后末梢的有效机制与功能性线粒体一样重要。除了线粒体膜电位的变化外，线粒体运动范围还受细胞骨架蛋白和运动蛋白磷酸化的调节。运动方向由血清素和多巴胺水平调节。然而，关于线粒体运动缺陷及其参与缺陷信号传导和神经可塑性与情绪障碍的关系的数据很少。我们之前已经报道了锂、丙戊酸盐和新型抗精神病药帕利哌酮对突触水平蛋白表达水平的影响。线粒体功能缺陷最近被认为与精神分裂症和双相情感障碍有关。我们假设情绪稳定剂治疗对线粒体功能、突触可塑性、线粒体迁移和运动方向有深远的影响。每天腹膜内注射锂、丙戊酸盐和帕利哌酮28次后，从大鼠前额叶皮质获得突触神经体制备物。使用2D-DIGE和纳米LC-ESI串联质谱鉴定磷酸化蛋白质。锂、丙戊酸盐和帕利哌酮对特定肌动蛋白、微管蛋白和肌球蛋白亚型以及其他与神经丝相关的蛋白质的磷酸化状态具有实质性和共同影响。此外，从复合物III和V的电子转移链的不同亚基严重磷酸化的治疗与这些药物表明选择性磷酸化。情绪稳定剂对线粒体功能、线粒体运动和这种运动的方向有影响。这些研究结果的影响将有助于新的见解有关的临床治疗和这些药物的作用模式。
Mitochondrial short and long-range movements are necessary to generate the energy needed for synaptic signaling and plasticity. Therefore, an effective mechanism to transport and anchor mitochondria to pre- and post-synaptic terminals is as important as functional mitochondria in neuronal firing. Mitochondrial movement range is regulated by phosphorylation of cytoskeletal and motor proteins in addition to changes in mitochondrial membrane potential. Movement direction is regulated by serotonin and dopamine levels. However, data on mitochondrial movement defects and their involvement in defective signaling and neuroplasticity in relationship with mood disorders is scarce. We have previously reported the effects of lithium, valproate and a new antipsychotic, paliperidone on protein expression levels at the synaptic level. Mitochondrial function defects have recently been implicated in schizophrenia and bipolar disorder. We postulate that mood stabilizer treatment has a profound effect on mitochondrial function, synaptic plasticity, mitochondrial migration and direction of movement. Synaptoneurosomal preparations from rat pre-frontal cortex were obtained after 28 daily intraperitoneal injections of lithium, valproate and paliperidone. Phosphorylated proteins were identified using 2D-DIGE and nano LC-ESI tandem mass spectrometry. Lithium, valproate and paliperidone had a substantial and common effect on the phosphorylation state of specific actin, tubulin and myosin isoforms as well as other proteins associated with neurofilaments. Furthermore, different subunits from complex III and V of the electron transfer chain were heavily phosphorylated by treatment with these drugs indicating selective phosphorylation. Mood stabilizers have an effect on mitochondrial function, mitochondrial movement and the direction of this movement. The implications of these findings will contribute to novel insights regarding clinical treatment and the mode of action of these drugs.
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影响因子：
3
作者：
Benitez-King, G.;Ramirez-Rodriguez, G.;Meza, I
通讯作者：
Meza, I
影响因子：
3.4
作者：
English, Jane A.;Dicker, Patrick;Cotter, David R.
通讯作者：
Cotter, David R.
DOI：
10.1083/jcb.200212140
发表时间：
2003-05-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bloom O;Evergren E;Tomilin N;Kjaerulff O;Löw P;Brodin L;Pieribone VA;Greengard P;Shupliakov O
通讯作者：
Shupliakov O
突触时的钙粘蛋白和Catenin：突触发生和突触可塑性中的作用。
影响因子：
15.9
作者：
Arikkath, Jyothi;Reichardt, Louis F.
通讯作者：
Reichardt, Louis F.
影响因子：
2.7
作者：
Ali, Shoukath M.;Ahmad, Ateeq;Ahmad, Imran
通讯作者：
Ahmad, Imran