Jafferali S, Dumont Y, Sotty F, Robitaille Y, Quirion R, Kar S
Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal, Canada.
Synapse. 2000 Dec 15;38(4):450-9. doi: 10.1002/1098-2396(20001215)38:4<450::AID-SYN10>3.0.CO;2-J.
Assimilated evidence indicates that the neurotoxic potential of amyloid beta (Abeta) peptide and an alteration in the level of growth factor(s) may possibly be involved in the loss of neurons observed in the brain of patients suffering from Alzheimer disease (AD), the prevalent cause of dementia in the elderly. In the present study, using receptor binding assays and immunocytochemistry, we evaluated the pharmacological profile of insulin-like growth factor-I (IGF-I) receptors and the distribution of IGF-I immunoreactivity in the frontal cortex, hippocampus, and cerebellum of AD and age-matched control brains. In control brains, [(125)I]IGF-I binding was inhibited more potently by IGF-I than by Des(1-3)IGF-I, IGF-II or insulin. The IC(50) values for IGF-I in the frontal cortex, hippocampus, and cerebellum of the normal brain did not differ significantly from the corresponding regions of the AD brain. Additionally, neither K(D) nor B(max) values were found to differ in the hippocampus of AD brains from the controls. At the regional levels, [(125)I]IGF-I binding sites in the AD brain also remained unaltered compared to the controls. As for the peptide itself, IGF-I immunoreactivity, in normal control brains, was evident primarily in a subpopulation of astrocytes in the frontal cortex and hippocampus, and in certain Purkinje cells of the cerebellum. In AD brains, a subset of Abeta-containing neuritic plaques, apart from astrocytes, exhibit IGF-I immunoreactivity. These results, taken together, suggest a role for IGF-I in compensatory plasticity and/or survival of the susceptible neurons in AD brains.
已吸收的证据表明，β淀粉样蛋白（Aβ）肽的神经毒性潜能以及生长因子水平的改变可能与阿尔茨海默病（AD）患者大脑中观察到的神经元丧失有关，AD是老年人痴呆的常见病因。在本研究中，我们使用受体结合测定和免疫细胞化学方法，评估了胰岛素样生长因子-I（IGF-I）受体的药理学特征以及IGF-I免疫反应性在AD大脑和年龄匹配的对照大脑的额叶皮质、海马体和小脑中的分布。在对照大脑中，[125I]IGF-I结合被IGF-I抑制的效力比被去（1-3）IGF-I、IGF-II或胰岛素抑制的效力更强。正常大脑额叶皮质、海马体和小脑中IGF-I的IC50值与AD大脑的相应区域没有显著差异。此外，AD大脑海马体中的KD值和Bmax值与对照组相比也没有差异。在区域水平上，与对照组相比，AD大脑中的[125I]IGF-I结合位点也保持不变。至于肽本身，在正常对照大脑中，IGF-I免疫反应性主要在额叶皮质和海马体的星形胶质细胞亚群以及小脑的某些浦肯野细胞中明显。在AD大脑中，除了星形胶质细胞外，一部分含有Aβ的神经炎性斑块也表现出IGF-I免疫反应性。综合这些结果，表明IGF-I在AD大脑中易感神经元的代偿性可塑性和/或存活中发挥作用。
