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大脑 IGF-I 调节 LTP、空间记忆和性别二态行为。

Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior.

机构信息

Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.

CIBERNED, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.

出版信息

Life Sci Alliance. 2023 Jul 18;6(10). doi: 10.26508/lsa.202201691. Print 2023 Oct.

DOI:10.26508/lsa.202201691
PMID:37463753
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10355288/
Abstract

Insulin-like growth factor-I (IGF-I) exerts multiple actions, yet the role of IGF-I from different sources is poorly understood. Here, we explored the functional and behavioral consequences of the conditional deletion of in the nervous system ( ), and demonstrated that long-term potentiation was impaired in hippocampal slices. Moreover, mice showed spatial memory deficits in the Morris water maze, and the significant sex-dependent differences displayed by mice disappeared in mice in the open field and rota-rod tests. Brain deletion disorganized the granule cell layer of the dentate gyrus (DG), and it modified the relative expressions of GAD and VGLUT1, which are preferentially localized to inhibitory and excitatory presynaptic terminals. Furthermore, deletion altered protein modules involved in receptor trafficking, synaptic proteins, and proteins that functionally interact with estrogen and androgen metabolism. Our findings indicate that brain IGF-I is crucial for long-term potentiation, and that it is involved in the regulation of spatial memory and sexual dimorphic behaviors, possibly by maintaining the granule cell layer structure and the stability of synaptic-related protein modules.

摘要

胰岛素样生长因子-I（IGF-I）发挥多种作用，但不同来源的 IGF-I 的作用尚不清楚。在这里，我们探索了神经系统条件性缺失（）的功能和行为后果，并表明海马切片中的长时程增强受损。此外，在 Morris 水迷宫中，IGF-I 缺失的小鼠表现出空间记忆缺陷，而在旷场和转棒测试中，IGF-I 缺失的雄性和雌性小鼠之间的显著性别依赖性差异在 IGF-I 缺失的雄性和雌性小鼠中消失。大脑 IGF-I 缺失打乱了齿状回的颗粒细胞层，并改变了优先定位于抑制性和兴奋性突触前末端的 GAD 和 VGLUT1 的相对表达。此外，缺失改变了参与受体运输、突触蛋白以及与雌激素和雄激素代谢功能相互作用的蛋白质模块。我们的研究结果表明，大脑 IGF-I 对于长时程增强至关重要，并且它参与了空间记忆和性别二态行为的调节，可能通过维持颗粒细胞层结构和突触相关蛋白模块的稳定性来实现。

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