RESEARCH OF NOVEL GENES PROMOTING NEURONAL PLASTISITY IN ANIMAL MODEL OF HYPERTROPHIC HIPPOCAMPAL GRANULE CELLS

亚毒性剂量的海人酸海人酸(KA)在小鼠海马区注射可引起齿状回颗粒细胞的弥散和肥大改变。这些形态变化持续时间较长，脑源性神经营养因子(BDNF)水平明显升高，而以往的研究结果表明，BDNF仅与肥大的发生有关。因此，应该存在一些其他因素来支持这种肥厚性改变。为了寻找其他影响因素，本研究利用差异显示聚合酶链式反应技术研究了KA注射后亚急性期和慢性期信使RNA的表达。在注射KA后2周和8周，有5条条带被差异显示，并进行了测序，其中4条被认为是非特异性的。其余1个基因全长为500bp，与人脑cDNA文库中鉴定的KIAA0279基因同源。原位杂交研究表明，该基因在肥大颗粒细胞中表达较强。Northern印迹分析表明，该基因不仅存在于脑中，而且在其他器官中也存在，其长度约为2kbp。在脑内，该基因不仅在肥大颗粒细胞中表达，在齿状颗粒细胞、小脑颗粒细胞中也有中等表达，在全脑中表达较弱。虽然不能在大鼠体内诱导肥大，但该基因在大鼠和小鼠中都有表达。发育研究表明，该基因在皮质板中观察到，随着发育的推进而减少。这些结果表明，该基因不仅与肥大本身有关，而且与神经元的发育和可塑性普遍相关。

Intrahippocampal injection of a subtoxic dose of kainate (KA) in mice has been shown to induce a dispersion and a hypertrophic change of granule cells of the dentate gyrus. These morphological changes are long-lasting with conspicuous increases of brain-derived neurotrophic factor (BDNF).Whereas, the previous results indicated that BDNF was related only with the initiation of hypertrophy. Therefore, some other factors should exist to support this hypertrophic change. To find the other factors, in this study we investigated the messenger RNA expression in subacute and chronic phases after KA injection by differential display PCR.Five bands were differentially displayed both in 2 and 8 weeks after KA injection and sequenced but four out of five were thought as non-specific. One remaining gene was 500 bp, and was homologous with KIAA0279 that was identified from human brain cDNA library. In situ hybridization studies revealed that the gene was expressed stronger in the hypertrophic granule cells. A Northern blot analysis showed that the gene existed not only in brain and but also in the other organs, and its length was about 2kbp. In the brain, the gene was expressed not only in the hypertrophic granule cells but also expressed moderately in the dentate granule cells, cerebeller granule cells, and weakly in the whole brain. Although the hypertrophy could not be induced in rat, the gene was expressed in rat like as mouse. Development study showed that the gene was observed in the cortical plate that reduced with the advancement of the development. These results suggested that this gene is not specifically related to the hypertrophy itself but also related generally to the neuronal development and plasticity.