Niblock M M, Brunso-Bechtold J K, Riddle D R
Department of Neurobiology and Anatomy and Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1010, USA.
J Neurosci. 2000 Jun 1;20(11):4165-76. doi: 10.1523/JNEUROSCI.20-11-04165.2000.
The temporal and spatial distributions of several growth factors suggest roles in the regulation of neuronal differentiation in the neocortex. Among such growth factors, the insulin-like growth factors (IGF-I and -II) are of particular interest because they are available to neurons from multiple sources under independent control. IGF-I is produced by many neurons throughout the brain and also by cells in the cerebral vasculature. IGF-II is found at high levels in the CSF, and both IGF-I and IGF-II cross the blood-brain barrier. Thus, the IGFs may act as both paracrine and endocrine regulators of neuronal development. As an initial step toward understanding the influence of IGFs in the developing cerebral cortex, the present study examined the effects of IGF-I and of the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) on the dendritic complexity of layer 2 pyramidal neurons. The results demonstrate that IGF-I increased the branching and total extent of both apical and basal dendrites of pyramidal cells in organotypic slices of rat primary somatosensory cortex. BDNF and NT-3 also enhanced dendritic development, but the two neurotrophins increased the extent of only basal, not apical, dendrites and promoted greater elongation than was seen after IGF-I treatment. These results provide direct evidence that IGF-I can regulate the dendritic elaboration of cortical neurons and indicate that endogenous IGFs may influence dendritic differentiation and the formation of cortical connections. In addition, IGF-dependent regulation of dendritic structure may represent a link between age-related declines in IGFs and cognitive deficits seen in senescence.
几种生长因子的时空分布表明其在新皮质神经元分化调控中发挥作用。在这些生长因子中，胰岛素样生长因子（IGF-I和IGF-II）尤为引人关注，因为它们可从多个独立控制的来源供神经元利用。IGF-I由全脑的许多神经元以及脑血管中的细胞产生。IGF-II在脑脊液中含量很高，IGF-I和IGF-II均可穿过血脑屏障。因此，IGF可能作为神经元发育的旁分泌和内分泌调节因子。作为了解IGF对发育中的大脑皮质影响的第一步，本研究检测了IGF-I以及神经营养因子脑源性神经营养因子（BDNF）和神经营养因子-3（NT-3）对第2层锥体神经元树突复杂性的影响。结果表明，IGF-I增加了大鼠初级体感皮质器官型切片中锥体细胞顶树突和基底树突的分支及总长度。BDNF和NT-3也增强了树突发育，但这两种神经营养因子仅增加了基底树突而非顶树突的长度，且比IGF-I处理后促进了更大程度的伸长。这些结果提供了直接证据，证明IGF-I可调节皮质神经元的树突细化，并表明内源性IGF可能影响树突分化和皮质连接的形成。此外，IGF依赖的树突结构调节可能代表了IGF与衰老中出现的认知缺陷相关的年龄相关下降之间的联系。
