Cyclin D1 in excitatory neurons of the adult brain enhances kainate-induced neurotoxicity
Cyclin D1 in excitatory neurons of the adult brain enhances kainate-induced neurotoxicity
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DOI：
10.1016/j.nbd.2008.04.010
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发表时间：
2008-08-01
影响因子：
6.1
通讯作者：
Glickstein, Sara B.
中科院分区：
文献类型：
--
作者：
Koeller, Hajira B.;Ross, M. Elizabeth;Glickstein, Sara B.
G1期细胞周期蛋白D1(CD1)在细胞有丝分裂后神经元中的表达已被证实，这导致了其他人提出，试图重新进入细胞周期可能会导致细胞死亡。在这里，CD1免疫反应在整个大脑的健康兴奋性神经元亚群中被发现。最引人注目的是CD1在海马锥体神经元中的选择性表达，这是一个特别脆弱的细胞组。应用红藻氨酸(KA)或戊四氮(PTZ)对CD1杂合子(+/-)和野生型小鼠进行致痫阈值、CD1诱导和CA1神经元死亡的检测，以确定基线CD1是否与病理相关。与野生型相比，CD1+/-小鼠表现出对KA的抵抗力，但不能抵抗PTZ诱导的癫痫发作，并且细胞毒性分别降低或相当。KA可诱导CD1的表达，而PTZ则不能。这些发现表明，尽管CD1不是细胞凋亡的直接沉淀物，但CD1的基础表达可能使海马环路更容易受到特定致痫药物和兴奋性毒性细胞死亡的影响。(C)2008 Elsevier Inc.保留所有权利。
G1-phase cyclin D1 (cD1) expression has been documented in post-mitotic neurons undergoing apoptosis, leading others to propose that attempted cell cycle re-entry may induce cell death. Here, cD1 immunoreactivity was found in a subpopulation of healthy excitatory neurons throughout the brain. Most striking was the selective cD1 expression in hippocampal pyramidal neurons, an especially vulnerable cell group. Seizure threshold, cD1 induction and CA1 neuron death were examined following application of kainate (KA) or pentylenetetrazole (PTZ) in cD1 heterozygous (+/-) and wildtype mice to determine whether baseline cD1 correlates with pathology. cD1+/- mice displayed resistance to KA, but not PTZ-induced seizures and had reduced or equivalent cytotoxicity respectively, compared with wildtype. KA administration, but not PTZ, induced cD1 expression. These findings suggest that basal cD1 expression may render hippocampal circuits more susceptible to particular epileptogenic agents and excitotoxic cell death, though cD1 is not a direct precipitant in apoptosis. (C) 2008 Elsevier Inc. All rights reserved.