Li Chenchen, Li Xinmei, Chen Weiheng, Yu Shanshan, Chen Jutao, Wang Huili, Ruan Diyun
Department of Neurobiology and Biophysics, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, PR China.
BMC Dev Biol. 2007 May 30;7:57. doi: 10.1186/1471-213X-7-57.
Cell-cycle-related proteins, such as cyclins or cyclin-dependent kinases, may have functions beyond that of cell cycle regulation. The expression and translocation of cyclinD1-CDK4 in post-mitotic neurons indicate that they may have supplementary functions in differentiated neurons that might be associated with neuronal plasticity.
In the present study, our findings showed that the expression of CDK4 was localized mostly in nuclei and cytoplasm of pyramidal cells of CA1 at postnatal day 10 (P10); whereas at P28 staining of CDK4 could be detected predominantly in the cytoplasm but not nuclei. Basal synaptic transmission was normal in the presence of CDK4 inhibitor. Short-term synaptic plasticity (STP) was impaired in CDK4 inhibitor pre-treated slices both from neonatal (P8-15) and adolescent (P21-35) animals; however there was no significant change in paired-pulse facilitation (PPF) in slices pre-incubated with the CDK4 inhibitor from adolescent animals. By the treatment of CDK4 inhibitor, the induction or the maintenance of Long-term potentiation (LTP) in response to a strong tetanus and NMDA receptor-dependent long-term depression (LTD) were normal in hippocampus. However, long-term depression (LTD) induced either by group I metabotropic glutamate receptors (mGluRs) agonist or by paired-pulse low-frequency stimulation (PP-LFS) was impaired in CDK4 inhibitor pretreated slices both from neonatal and adolescent animals. But the effects of the CDK4 inhibitor at slices from adolescent animals were not as robust as at slices from neonatal animals.
Our results indicated that the activation of cyclinD1-CDK4 is required for short-term synaptic plasticity and mGluR-dependent LTD, and suggested that this cyclin-dependent kinase may have different roles during the postnatal development in mice hippocampus area CA1.
细胞周期相关蛋白，如细胞周期蛋白或细胞周期蛋白依赖性激酶，可能具有细胞周期调控以外的功能。细胞周期蛋白D1 - 细胞周期蛋白依赖性激酶4（cyclinD1 - CDK4）在有丝分裂后神经元中的表达和易位表明，它们可能在分化的神经元中具有与神经可塑性相关的补充功能。
在本研究中，我们的发现表明，出生后第10天（P10）时，CDK4的表达主要定位于CA1区锥体细胞的细胞核和细胞质中；而在P28时，CDK4染色主要在细胞质中检测到，而不在细胞核中。在存在CDK4抑制剂的情况下，基础突触传递正常。来自新生（P8 - 15）和青春期（P21 - 35）动物的CDK4抑制剂预处理切片中的短期突触可塑性（STP）受损；然而，用来自青春期动物的CDK4抑制剂预孵育的切片中，双脉冲易化（PPF）没有显著变化。通过CDK4抑制剂处理，海马体中对强强直刺激的长时程增强（LTP）的诱导或维持以及NMDA受体依赖性长时程抑制（LTD）均正常。然而，来自新生和青春期动物的CDK4抑制剂预处理切片中，由I组代谢型谷氨酸受体（mGluRs）激动剂或双脉冲低频刺激（PP - LFS）诱导的长时程抑制（LTD）受损。但是CDK4抑制剂对青春期动物切片的影响不如对新生动物切片的影响强烈。
我们的结果表明，细胞周期蛋白D1 - CDK4的激活是短期突触可塑性和mGluR依赖性LTD所必需的，并表明这种细胞周期蛋白依赖性激酶在小鼠海马体CA1区出生后发育过程中可能具有不同作用。
