Lu X R, Ong W Y
Department of Anatomy, National University of Singapore, Singapore 119260.
Exp Brain Res. 2001 Apr;137(3-4):424-31. doi: 10.1007/s002210000616.
The present study aimed to elucidate the distribution of heme oxygenase-1 (HO-1) in the hippocampus after intracerebroventricular injections of kainate. Very little or no staining of HO-1 was observed in the normal CA1, whilst moderate staining of dentate hilar neurons was observed in the dentate gyrus, in the normal hippocampus. At postinjection day 1, a slight increase in immunoreactivity in the neuropil of the lesioned CA fields and a marked increase in HO-1 immunoreactivity in glial cells of the stratum lacunosum moleculare of CA fields and the stratum moleculare of the dentate gyrus was observed. Electron microscopy showed that the glial cells had features of viable astrocytes. At postinjection day 3, glial cells in the dentate gyrus continued to express HO-1, whilst pyramidal neurons in the degenerating CA fields started to express intense HO-1 immunoreactivity in their cell bodies. At postinjection weeks 1-3, HO-1 was observed in glial cells in the center of the lesion, but also in neurons at the perifocal region of the glial scar. The glial cells were found to have features of viable astrocytes and microglia, whilst the neurons contained discontinuous cell membranes and nuclear outlines, and had features of degenerating neurons. Intense immunoreactivity was observed in the cytoplasm of the degenerating neurons. The density of staining was greater than that observed in astrocytes or microglia. Recent in vitro results on fibroblasts transfected with HO-1 cDNA showed that, despite cytoprotection with low (less than fivefold compared with untransfected cells) HO-1 activity, high levels of HO-1 expression (more than 15-fold) were associated with significant oxygen toxicity. These and the present observations suggest a destructive effect of increased expression of HO-1 in neurons, and possible novel therapeutic approaches involving overexpression of HO-1 must therefore be approached with caution.
本研究旨在阐明脑室内注射红藻氨酸后海马中血红素加氧酶-1（HO-1）的分布情况。在正常海马中，正常CA1区几乎未观察到HO-1染色或无染色，而在齿状回中齿状门区神经元有中度染色。注射后第1天，损伤CA区神经毡中免疫反应性略有增加，CA区分子层和齿状回分子层的胶质细胞中HO-1免疫反应性显著增加。电子显微镜显示这些胶质细胞具有活星形胶质细胞的特征。注射后第3天，齿状回中的胶质细胞继续表达HO-1，而退化CA区的锥体神经元开始在其细胞体中表达强烈的HO-1免疫反应性。注射后1 - 3周，在损伤中心的胶质细胞中观察到HO-1，同时在胶质瘢痕灶周区域的神经元中也观察到HO-1。发现胶质细胞具有活星形胶质细胞和小胶质细胞的特征，而神经元的细胞膜和核轮廓不连续，具有退化神经元的特征。在退化神经元的细胞质中观察到强烈的免疫反应性。染色密度大于星形胶质细胞或小胶质细胞中的观察结果。最近对用HO-1 cDNA转染的成纤维细胞的体外研究结果表明，尽管低水平（与未转染细胞相比小于5倍）的HO-1活性具有细胞保护作用，但高水平（超过15倍）的HO-1表达与显著的氧毒性相关。这些以及本研究的观察结果表明HO-1在神经元中表达增加具有破坏作用，因此涉及HO-1过表达可能的新治疗方法必须谨慎对待。
