MKK7 deficiency in mature neurons impairs parental behavior in mice.
MKK7 deficiency in mature neurons impairs parental behavior in mice.
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DOI：
10.1111/gtc.12816
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Nishina H
中科院分区：
文献类型：
--
作者：
Shin T;Hiraoka Y;Yamasaki T;Marth JD;Penninger JM;Kanai-Azuma M;Tanaka K;Kofuji S;Nishina H
C-Jun氨基末端激酶(JNKs)在哺乳动物大脑中被结构性激活，对它们的发育和神经功能是不可或缺的。MKK7是所有JNK的上游激活剂。然而，共同的JNK信号通路是否调节大脑对社会行为的控制仍不清楚。在这里，我们展示了在成熟神经元中特定缺失MKK7的雌性小鼠(Mkk7flx/FloxSyn-Cre小鼠)生下了正常数量的小鼠，但由于取回幼崽的缺陷而无法饲养它们。为了探索这种异常的机制，我们进行了全面的行为测试。Mkk7Flox/FloxSyn-Cre小鼠表现出正常的运动功能和认知能力，但表现出抑郁样行为。对突变脑的基因芯片分析显示，基因表达模式发生了变化。定量RT-PCR分析表明，神经信号通路和钙通道相关基因的mRNA表达水平与对照组有显著差异。此外，神经MKK7的缺失对少突胶质细胞的基因表达模式具有意想不到的调节作用。这些发现表明，MKK7在调节基因表达模式方面具有重要作用，这些基因表达模式负责促进正常的社会行为和防止抑郁。C-Jun氨基末端激酶(JNK)信号转导通路在哺乳动物脑发育和神经功能中发挥着重要作用。然而，丝裂原活化蛋白激酶7(MKK7)是JNK上游的一种特异性激活物，是否调节社会行为尚不清楚。在这项研究中，我们证明了成熟神经元中的MKK7-JNK通路调节小鼠的精神状态，并在父母行为中发挥关键作用。
c‐Jun N‐terminal kinases (JNKs) are constitutively activated in mammalian brains and are indispensable for their development and neural functions. MKK7 is an upstream activator of all JNKs. However, whether the common JNK signaling pathway regulates the brain's control of social behavior remains unclear. Here, we show that female mice in which Mkk7 is deleted specifically in mature neurons (Mkk7flox/floxSyn‐Cre mice) give birth to a normal number of pups but fail to raise them due to a defect in pup retrieval. To explore the mechanism underlying this abnormality, we performed comprehensive behavioral tests. Mkk7flox/floxSyn‐Cre mice showed normal locomotor functions and cognitive ability but exhibited depression‐like behavior. cDNA microarray analysis of mutant brain revealed an altered gene expression pattern. Quantitative RT‐PCR analysis demonstrated that mRNA expression levels of genes related to neural signaling pathways and a calcium channel were significantly different from controls. In addition, loss of neural MKK7 had unexpected regulatory effects on gene expression patterns in oligodendrocytes. These findings indicate that MKK7 has an important role in regulating the gene expression patterns responsible for promoting normal social behavior and staving off depression. c‐Jun N‐terminal kinase (JNK) signaling has well established, important roles in mammalian brain development and neural functions. However, whether the mitogen‐activated protein kinase kinase 7 (MKK7), a specific upstream activator of JNK, regulates social behavior remains unclear. In this study, we demonstrate that the MKK7‐JNK pathway in mature neurons regulates mouse mental status and plays a critical role in parental behavior.
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DOI：
10.1073/pnas.96.22.12905
发表时间：
1999-10-26
影响因子：
11.1
作者：
Mihalek, RM;Banerjee, PK;Homanics, GE
通讯作者：
Homanics, GE
DOI：
10.1038/npp.2015.26
发表时间：
2015-06
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Aida T;Yoshida J;Nomura M;Tanimura A;Iino Y;Soma M;Bai N;Ito Y;Cui W;Aizawa H;Yanagisawa M;Nagai T;Takata N;Tanaka KF;Takayanagi R;Kano M;Götz M;Hirase H;Tanaka K
通讯作者：
Tanaka K
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
影响因子：
3.3
作者：
Belelli, D;Herd, MB;Lambert, JJ
通讯作者：
Lambert, JJ
影响因子：
2.9
作者：
MAURICE, T;HIRAMATSU, M;NABESHIMA, T
通讯作者：
NABESHIMA, T