Lindefors N, Brodin E, Metsis M
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Neuroscience. 1995 Apr;65(3):661-70. doi: 10.1016/0306-4522(94)00550-o.
Electroconvulsive therapy is used in the treatment of affective disorders and schizophrenia and experimental electroconvulsive shock may serve as an animal model for this treatment. The aim of this study was to investigate a possible role for neurotrophins in the mechanism of action of experimental electroconvulsive shock and thus in clinical electroconvulsive therapy. The effect of electroconvulsive shock on levels of messenger RNAs encoding the neurotrophin brain-derived neurotrophic factor and the receptor trkB in rat hippocampus was determined by in situ hybridization with RNA probes 1, 3, 9 and 27 h following the shock. Brain-derived neurotrophic factor messenger RNA levels were increased at 1, 3 and 9 h following the shock and normalized after 27 h. Granule cells of the dentate gyrus showed a more rapid response as compared to hilar cells and pyramidal cells of CA1. Total trkB messenger RNA levels, including the transcripts for both the truncated and full length trkB receptor protein (gp95trkB and gp145trkB, respectively), showed a pattern of increase very similar to that of the brain-derived neurotrophic factor messenger RNA. However, using a probe selective for the full length (gp145trkB) trkB messenger RNA, we determined a delayed pattern of activation with significant increase only at 3 and 9 h after the shock. In hippocampus total trkB messenger RNA was found to consist of approximately one-quarter of mRNA encoding gp145trkB and three-quarters encoding gp95trkB as revealed by RNAase protection. While brain-derived neurotrophic factor and the truncated trkB messenger RNAs appear to increase with a similar pattern, suggesting a similar mechanism of activation by electroconvulsive shock, full length receptor trkB messenger RNA appears to increase with a delayed pattern suggesting a separate mechanism of activation. Electroconvulsive shock-induced seizures seem to include activation of a brain neurotrophin known to be important for neuronal plasticity.
电休克疗法用于治疗情感障碍和精神分裂症，实验性电休克可作为该治疗方法的动物模型。本研究的目的是探讨神经营养因子在实验性电休克作用机制中以及在临床电休克治疗中的可能作用。通过在电休克后1、3、9和27小时用RNA探针进行原位杂交，测定电休克对大鼠海马中编码神经营养因子脑源性神经营养因子及其受体trkB的信使RNA水平的影响。脑源性神经营养因子信使RNA水平在电休克后1、3和9小时升高，27小时后恢复正常。与齿状回门区细胞和CA1区锥体细胞相比，齿状回颗粒细胞的反应更快。总trkB信使RNA水平，包括截短型和全长trkB受体蛋白（分别为gp95trkB和gp145trkB）的转录本，显示出与脑源性神经营养因子信使RNA非常相似的升高模式。然而，使用对全长（gp145trkB）trkB信使RNA具有选择性的探针，我们确定了一种延迟激活模式，仅在电休克后3和9小时显著增加。通过核糖核酸酶保护分析发现，在海马中，总trkB信使RNA约四分之一由编码gp145trkB的mRNA组成，四分之三由编码gp95trkB的mRNA组成。虽然脑源性神经营养因子和截短型trkB信使RNA似乎以相似模式增加，提示电休克激活机制相似，但全长受体trkB信使RNA似乎以延迟模式增加，提示激活机制不同。电休克诱导的癫痫发作似乎包括对一种已知对神经元可塑性很重要的脑神经营养因子的激活。
