Carboxypeptidase E knockout mice exhibit abnormal dendritic arborization and spine morphology in central nervous system neurons.

Carboxypeptidase E knockout mice exhibit abnormal dendritic arborization and spine morphology in central nervous system neurons.
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羧肽酶 E 敲除小鼠在中枢神经系统神经元中表现出异常的树突状树枝化和脊柱形态。

DOI:
10.1002/jnr.22174
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发表时间:
2010-01
影响因子:
4.2
通讯作者:
Loh, Y. Peng
Loh, Y. Peng
中科院分区:
医学3区
文献类型:
--
作者:
Woronowicz, Alicja;Cawley, Niamh X.;Chang, Su-Youne;Koshimizu, Hisatsugu;Phillips, Andre W.;Xiong, Zhi-Gang;Loh, Y. Peng

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羧肽酶E(Carboxypeptidase E,CPE)参与神经肽的成熟和脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的分选,以调节CNS神经元的活性依赖性分泌途径。CPE敲除(CPE-KO)小鼠具有许多神经缺陷,包括学习和记忆。在这里,我们分析了CPE-KO小鼠的树突状分支和脊柱形态,以确定这些结构中的缺陷与在这些动物中观察到的神经功能缺损的可能相关性。14周龄CPE-KO小鼠大脑皮质V层和海马CA 1区锥体神经元的分析显示,与野生型(WT)小鼠相比,树突更复杂。与WT神经元相比,CPE-KO有更多的树突交叉点和更多的分支点。6周龄与14周龄WT小鼠的锥体皮质神经元的比较显示树突分支减少,反映了正常树突修剪的发生。然而,这并没有发生在CPE-KO神经元。此外,棘形态学的分析表明,在CPE-KO动物的皮质神经元中被认为是无功能的D型棘的数量显著增加。我们的研究结果表明,CPE是一个重要的新球员在介导适当的树突状图案和脊柱形成中枢神经系统神经元。
Carboxypeptidase E (CPE) is involved in maturation of neuropeptides and sorting of brain-derived neurotrophic factor (BDNF) to the regulated pathway for activity-dependent secretion from CNS neurons. CPE knock-out (CPE-KO) mice have many neurological deficits including learning and memory. Here, we analyzed the dendritic arborization and spine morphology of CPE-KO mice to determine a possible correlation of defects in such structures with the neurological deficits observed in these animals. Analysis of pyramidal neurons in layer V of cerebral cortex and in hippocampal CA1 region in 14 week old CPE-KO mice showed more dendritic complexity compared to wild type (WT) mice. There were more dendritic intersections and more branch points in CPE-KO versus WT neurons. Comparison of pyramidal cortical neurons in 6 week versus 14 week old WT mice showed a decrease in dendritic arborization, reflecting the occurrence of normal dendritic pruning. However, this did not occur in CPE-KO neurons. Furthermore, analysis of spine morphology demonstrated a significant increase in the number of D-type spines regarded as non-functional in the cortical neurons of CPE-KO animals. Our findings suggest that CPE is an important novel player in mediating appropriate dendritic patterning and spine formation in CNS neurons.
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