Kar S, Baccichet A, Quirion R, Poirier J
Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal, Canada.
Neuroscience. 1993 Jul;55(1):69-80. doi: 10.1016/0306-4522(93)90455-o.
The hippocampus can be induced by deafferentation to selectively reorganize its neuronal input. Entorhinal cortex lesion, which causes degeneration of the perforant pathway, evokes sprouting of septal afferents as well as glutamatergic commissural/associational fibers in the deafferentated zone of the molecular layer of the dentate gyrus. Although the process of reactive synaptogenesis that follows deafferentation has been extensively studied, at present little is known about its molecular basis and the mechanism of initiation. In this study, following unilateral lesion of the entorhinal cortex, the time-course of possible alterations of insulin-like growth factors I and II, and insulin binding sites were evaluated by in vitro quantitative receptor autoradiography. [125I]Insulin-like growth factor I receptor binding sites did not exhibit any significant variation between the contralateral and ipsilateral hippocampal formation at any time periods following lesion except in the molecular layer of the dentate gyrus (P < 0.05) at day 8. However, when compared with the unlesioned animals, a differential time-dependent response of [125I]insulin-like growth factor I binding sites was noted in selective layers of the hippocampus. [125I]Insulin-like growth factor II receptor binding sites showed a significant decrease (P < 0.05) in the ipsilateral granular cell layer of the dentate gyrus only at day 14 post lesion. Interestingly, compared to controls, a dramatic bilateral increase (P < 0.05) in [125I]insulin-like growth factor II binding was evident between days 1 and 8 in most layers of the hippocampal formation. A lesion-induced bilateral increase (P < 0.05) in [125I]insulin binding sites was evident in all layers of the hippocampus between two to eight days and at 30 days post lesion. In selective layers, however, a significant increase (P < 0.05) in [125I]insulin binding sites was also observed at days 1 and 14 after lesion. These results, which are compatible with the process of degeneration and/or sprouting of the terminal fibers, suggest possible involvement of insulin-like growth factors and insulin in the sequence of molecular events that occur to facilitate neuronal repair and to promote neuronal survival following entorhinal cortex lesion.
去传入神经支配可诱导海马选择性地重新组织其神经元输入。内嗅皮质损伤会导致穿通通路退化，引发齿状回分子层去传入神经支配区域内的隔区传入纤维以及谷氨酸能连合/联合纤维的发芽。尽管去传入神经支配后发生的反应性突触形成过程已得到广泛研究，但目前对其分子基础和起始机制知之甚少。在本研究中，在内嗅皮质单侧损伤后，通过体外定量受体放射自显影评估胰岛素样生长因子I和II以及胰岛素结合位点可能发生的变化的时间进程。损伤后任何时间段，除了第8天齿状回分子层（P < 0.05）外，[125I]胰岛素样生长因子I受体结合位点在对侧和同侧海马结构之间均未表现出任何显著差异。然而，与未损伤动物相比，在海马的选择性层中观察到[125I]胰岛素样生长因子I结合位点有不同的时间依赖性反应。[125I]胰岛素样生长因子II受体结合位点仅在损伤后第14天在同侧齿状回颗粒细胞层显示出显著降低（P < 0.05）。有趣的是，与对照组相比，在损伤后第1天至第8天期间，海马结构的大多数层中[125I]胰岛素样生长因子II结合明显出现双侧显著增加（P < 0.05）。损伤诱导的[125I]胰岛素结合位点在损伤后2至8天以及30天在海马的所有层中均出现双侧显著增加（P < 0.05）。然而，在选择性层中，损伤后第1天和第14天也观察到[125I]胰岛素结合位点显著增加（P < 0.05）。这些结果与终末纤维的退化和/或发芽过程一致，表明胰岛素样生长因子和胰岛素可能参与了在内嗅皮质损伤后为促进神经元修复和促进神经元存活而发生的分子事件序列。
