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

在小鼠海马内注射亚毒性剂量的海碱盐（KA）已被证明可诱导齿状回颗粒细胞的分散和肥厚变化。这些形态学变化是持久的，脑源性神经营养因子（BDNF）明显增加。然而，先前的结果表明BDNF仅与肥厚的发生有关。因此，应该存在一些其他因素来支持这种肥厚变化。为了寻找其他影响因素，本研究采用差异显示PCR方法研究了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个条带显示出差异，并进行了测序，但其中4个条带被认为是非特异性的。其中1个基因长度为500bp，与人脑cDNA文库中鉴定的KIAA0279同源。原位杂交研究表明，该基因在增生性颗粒细胞中表达较强。Northern blot分析表明，该基因不仅存在于大脑中，也存在于其他器官中，其长度约为2kbp。在大脑中，该基因不仅在增生性颗粒细胞中表达，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。该基因在小鼠等大鼠体内均有表达，但在大鼠体内不能诱导心肌肥大。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，该基因与神经元肥大本身并不特异性相关，但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.