Folli F, Ghidella S, Bonfanti L, Kahn C R, Merighi A
Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Mol Neurobiol. 1996 Oct;13(2):155-83. doi: 10.1007/BF02740639.
Several studies support the idea that the polypeptides belonging to the family of insulin and insulin-like growth factors (IGFs) play an important role in brain development and continue to be produced in discrete areas of the adult brain. In numerous neuronal populations within the olfactory bulb, the cerebral and cerebellar cortex, the hippocampus, some diencephalic and brainstem nuclei, the spinal cord and the retina, specific insulin and IGF receptors, as well as crucial components of the intracellular receptor signaling pathway have been demonstrated. Thus, mature neurons are endowed with the cellular machinery to respond to insulin and IGF stimulation. Studies in vitro and in vivo, using normal and transgenic animals, have led to the hypothesis that, in the adult brain, IGF-I not only acts as a trophic factor, but also as a neuromodulator of some higher brain functions, such as long-term potentiation and depression. Furthermore, a trophic effect on certain neuronal populations becomes clearly evident in the ischemic brain or neurodegenerative disorders. Thus, the analysis of the early intracellular signaling pathway for the insulin/IGF receptor family in the brain is providing us with new intriguing findings on the way the mammalian brain is sculpted and operates.
多项研究支持这样一种观点，即属于胰岛素和胰岛素样生长因子（IGF）家族的多肽在大脑发育中发挥重要作用，并在成年大脑的离散区域持续产生。在嗅球、大脑和小脑皮质、海马体、一些间脑和脑干核、脊髓和视网膜内的众多神经元群体中，已证实存在特定的胰岛素和IGF受体以及细胞内受体信号通路的关键组成部分。因此，成熟神经元具备对胰岛素和IGF刺激作出反应的细胞机制。使用正常和转基因动物进行的体外和体内研究得出了这样的假设：在成年大脑中，IGF-I不仅作为一种营养因子起作用，还作为某些高级脑功能（如长时程增强和抑制）的神经调节因子。此外，在缺血性脑或神经退行性疾病中，对某些神经元群体的营养作用变得明显。因此，对大脑中胰岛素/IGF受体家族早期细胞内信号通路的分析为我们提供了关于哺乳动物大脑的塑造和运作方式的新的有趣发现。
