Melatonin stimulates dendrite formation and complexity in the hilar zone of the rat hippocampus: participation of the Ca++/Calmodulin complex.
Melatonin stimulates dendrite formation and complexity in the hilar zone of the rat hippocampus: participation of the Ca++/Calmodulin complex.
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DOI：
10.3390/ijms16011907
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发表时间：
2015-01-16
影响因子：
5.6
通讯作者：
Benítez-King G
中科院分区：
文献类型：
--
作者：
Domínguez-Alonso A;Valdés-Tovar M;Solís-Chagoyán H;Benítez-King G
褪黑激素(Mel)是松果体合成的主要产物，刺激成人大脑神经发育的早期和晚期。MEL增加了海马门部和苔藓状神经元中树突的长度、厚度和复杂性。树突的形成涉及钙调素(CaM)依赖的激酶II(CaMKII)被CaM激活。以前的工作表明，MEL增加了CaM的合成和转位，提示MEL通过这一途径激活CaM依赖的酶。在这项工作中，我们研究了MEL是否通过激活CaMKII刺激成年大鼠海马器型培养中树突的形成。我们发现，CaMKII抑制剂KN-62取消了MEL对树突发生的刺激作用，并且MEL增加了海马片可溶部分中CaM的相对含量。此外，抑制PKC可抑制树突状细胞的形成，而MEL受体(MT1/2)的拮抗剂Luzindole可部分阻断MEL的作用。此外，在MEL的存在下，CaMKII和PKC的自磷酸化以及ERK1/2的磷酸化都增加。我们的结果表明，MEL通过CaMKII刺激树突的形成和CaM向可溶性部分的移位。MEL诱导的树突状细胞生成也需要PKC的激活，部分参与了MT1/2受体的信号转导。数据有力地表明，MEL可以通过增加CaM水平和激活CaMKII来修复神经精神疾病中发生的海马树突状细胞的丢失。
Melatonin (MEL), the main product synthesized by the pineal gland, stimulates early and late stages of neurodevelopment in the adult brain. MEL increases dendrite length, thickness and complexity in the hilar and mossy neurons of hippocampus. Dendrite formation involves activation of Ca2+/Calmodulin (CaM)-dependent kinase II (CaMKII) by CaM. Previous work showed that MEL increased the synthesis and translocation of CaM, suggesting that MEL activates CaM-dependent enzymes by this pathway. In this work we investigated whether MEL stimulates dendrite formation by CaMKII activation in organotypic cultures from adult rat hippocampus. We found that the CaMKII inhibitor, KN-62, abolished the MEL stimulatory effects on dendritogenesis and that MEL increased the relative amount of CaM in the soluble fraction of hippocampal slices. Also, PKC inhibition abolished dendritogenesis, while luzindole, an antagonist of MEL receptors (MT1/2), partially blocked the effects of MEL. Moreover, autophosphorylation of CaMKII and PKC was increased in presence of MEL, as well as phosphorylation of ERK1/2. Our results indicate that MEL stimulates dendrite formation through CaMKII and the translocation of CaM to the soluble fraction. Dendritogenesis elicited by MEL also required PKC activation, and signaling through MT1/2 receptors was partially involved. Data strongly suggest that MEL could repair the loss of hippocampal dendrites that occur in neuropsychiatric disorders by increasing CaM levels and activation of CaMKII.
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影响因子：
5.6
作者：
BABU, YS;BUGG, CE;COOK, WJ
通讯作者：
COOK, WJ
影响因子：
5.3
作者：
Fong, DK;Rao, A;Craig, AM
通讯作者：
Craig, AM
影响因子：
10.3
作者：
Dominguez-Alonso, Aline;Ramirez-Rodriguez, Gerardo;Benitez-King, Gloria
通讯作者：
Benitez-King, Gloria
影响因子：
4.1
作者：
GILLESPIE, CS;WILSON, R;BROPHY, PJ
通讯作者：
BROPHY, PJ
影响因子：
1.6
作者：
Dolek, N.;Saylisoy, S.;Adapinar, B.
通讯作者：
Adapinar, B.