Ong W Y, Leong S K, Garey L J, Reynolds R, Liang A W
Department of Anatomy, National University of Singapore.
Exp Brain Res. 1996 May;109(2):251-67. doi: 10.1007/BF00231785.
Immunocytochemistry was used to study the distribution of the kainate receptors GluR1, GluR2/3 and GluR4 and of the N-methyl-D-aspartate (NMDA) receptor NMDAR1 as well as the astrocyte markers glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP) in the hippocampus of normal and kainate-lesioned rats. Hippocampal pyramidal neurons and dentate granule neurons were labelled heavily for GluR1 and GluR2/3, but only lightly for GluR4. Dense GluR4 immunopositivity was, however, observed in oligodendrocyte-like glial cells. Hippocampal pyramidal neurons and dentate granule neurons were moderately labelled for NMDAR1. Intravenous kainate injections resulted in a decrease in GluR1 and GluR2/3 immunoreactivity on the apical dendrites of pyramidal neurons as early as 7 h postinjection. At 18 h, there was a marked reduction in GluR1 and GluR2/3 receptors in the terminal tuft of dendrites of most hippocampal pyramidal neurons in the affected area, although some cells showed labelling in other portions of the apical dendrites and in basal dendrites. Immunostaining for GluR4 and NMDAR1 was also reduced at this time. At postinjection day 3, only the cell bodies and the basal dendrites of a few scattered pyramidal cells were labelled. Taken together, these results indicate a progressive loss of glutamate receptors, which affects the apical dendritic tree before the basal dendritic tree. The decrease in receptor immunoreactivity could be due to a downregulation of the receptors, since it occurred as early as 7 h postlesion, before cell death was evident in Nissl-stained sections. At long intervals after kainate injection, all pyramidal cells at the centre of the lesion showed a lack of glutamate receptor staining, and no partially labelled pyramidal cells were observed. The periphery of the lesion, however, contained many partially labelled pyramidal neurons among the unlabelled cells and had features of early lesions. The present study also showed an early decrease in GS immunoreactivity in the affected CA fields of the hippocampus (18 h to 3 days postinjection), followed by a medium-term increase (5-68 days) and a late decrease in GS immunoreactivity (81 days). The decrease in GS immunoreactivity at 81 days is not due to an absence of astrocytes, since GFAP staining showed many densely labelled astrocytes in the affected CA field.
采用免疫细胞化学方法研究正常大鼠和经红藻氨酸损伤大鼠海马中红藻氨酸受体GluR1、GluR2/3和GluR4、N-甲基-D-天冬氨酸（NMDA）受体NMDAR1以及星形胶质细胞标志物谷氨酰胺合成酶（GS）和胶质纤维酸性蛋白（GFAP）的分布。海马锥体细胞和齿状颗粒细胞对GluR1和GluR2/3标记强烈，但对GluR4标记较弱。然而，在少突胶质细胞样神经胶质细胞中观察到密集的GluR4免疫阳性。海马锥体细胞和齿状颗粒细胞对NMDAR1标记中等。静脉注射红藻氨酸后，早在注射后7小时，锥体细胞顶端树突上的GluR1和GluR2/3免疫反应性就降低。在18小时时，受影响区域大多数海马锥体细胞树突终末丛中的GluR1和GluR2/3受体明显减少，尽管一些细胞在顶端树突的其他部分和基底树突中有标记。此时GluR4和NMDAR1的免疫染色也减少。在注射后第3天，只有少数散在的锥体细胞的胞体和基底树突有标记。综上所述，这些结果表明谷氨酸受体逐渐丧失，顶端树突先于基底树突受到影响。受体免疫反应性的降低可能是由于受体下调，因为早在损伤后7小时就出现了这种情况，此时尼氏染色切片中细胞死亡尚不明显。在注射红藻氨酸后的较长时间间隔内，损伤中心的所有锥体细胞均缺乏谷氨酸受体染色，未观察到部分标记的锥体细胞。然而，损伤周边在未标记的细胞中有许多部分标记的锥体细胞，具有早期损伤的特征。本研究还显示，海马受影响的CA区GS免疫反应性在早期降低（注射后18小时至3天），随后中期升高（5 - 68天），晚期降低（81天）。81天时GS免疫反应性降低并非由于星形胶质细胞缺失，因为GFAP染色显示受影响的CA区有许多密集标记的星形胶质细胞。
