Effect of kainic acid treatment on insulin-like growth factor-2 receptors in the IGF2-deficient adult mouse brain
Effect of kainic acid treatment on insulin-like growth factor-2 receptors in the IGF2-deficient adult mouse brain
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DOI：
10.1016/j.brainres.2006.11.022
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发表时间：
2007-02-02
期刊：
影响因子：
2.9
通讯作者：
Lopez, M. F.
中科院分区：
文献类型：
--
作者：
Dikkes, P.;Hawkes, C.;Lopez, M. F.
胰岛素样生长因子-2(IGF2)是胰岛素基因家族中的一员，具有已知的神经营养特性。IGF2的作用是通过IGF 1型和2型受体以及胰岛素受体介导的，所有这些受体在大脑中都广泛表达。由于IGF2在损伤后在大脑中上调，我们想确定IGF2的缺失是否会导致脑形态和/或其受体结合部位在神经毒性损伤后的反应发生任何变化。IGF2基因敲除小鼠(IGF2(-/-))和野生型对照(IGF2‘1’)小鼠的脑形态结构没有差异。然而，我们的体外受体放射自显影结果表明，与IGF2(+/+)小鼠相比，IGF2(-/-)小鼠在海马区和小脑的内源性[I-125]IGF1和[I-125]胰岛素受体结合部位的水平较低，而内源性[I-125]IGF2受体结合量仅在小脑中减少。给予海人酸后7d，IGF2(+/+)小鼠各脑区的[I-125]胰岛素受体结合位点显著减少，而[I-125]IGF1和[I-125]IGF2结合位点的水平仅在特定脑区减少。另一方面，IGF2(-/-)小鼠在海马体和小脑等特定区域显示[I-125]IGF1和[I-125]IGF2和[I-125]胰岛素受体结合位点增加。综上所述，这些结果表明IGF2基因的缺失不影响脑的大体形态，但选择性地改变内源性[I-125]IGF1、[I-125]IGF2和[I-125]胰岛素受体结合部位及其对神经毒性的反应。(C)2006爱思唯尔B.V.保留所有权利。
Insulin-like growth factor-2 (IGF2) is a member of the insulin gene family with known neurotrophic properties. The actions of IGF2 are mediated via the IGF type 1 and type 2 receptors as well as through the insulin receptors, all of which are widely expressed throughout the brain. Since IGF2 is up-regulated in the brain after injury, we wanted to determine whether the absence of IGF2 can lead to any alteration on brain morphology and/ or in the response of its receptor binding sites following a neurotoxic insult. No morphological differences were observed between the brains of IGF2 knockout (IGF2(-/-)) and wild-type control (IGF2'1') mice. However, our in vitro receptor autoradiography results indicate that IGF2(-/-) mice had lower endogenous levels of [I-125] IGF1 and [I-125] insulin receptor binding sites in the hippocampus and cerebellum as compared to IGF2(+/+) mice, while endogenous [I-125]IGF2 receptor binding showed a decrease only in the cerebellum. Seven days after kainic acid administration, the [I-125]insulin receptor binding sites were significantly decreased in all brain regions of the IGF2(+/+) mice, while the levels of [I-125]IGF1 and [I-125]IGF2 binding sites were decreased only in select brain areas. The IGF2(-/-) mice, on the other hand, showed increased [I-125]IGF1 and [I-125]IGF2 and [I-125]insulin receptor binding sites in selected regions such as the hippocampus and cerebellum. These results, taken together, suggest that deletion of IGF2 gene does not affect gross morphology of the brain but does selectively alter endogenous [I-125]IGF1, [I-125]IGF2 and [I-125] insulin receptor binding sites and their response to neurotoxicity. (c) 2006 Elsevier B.V. All rights reserved.