Breese C R, D'Costa A, Rollins Y D, Adams C, Booze R M, Sonntag W E, Leonard S
University of Colorado Health Sciences Center, Department of Pharmacology and Psychiatry, Denver 80262, USA.
J Comp Neurol. 1996 Jun 3;369(3):388-404. doi: 10.1002/(SICI)1096-9861(19960603)369:3<388::AID-CNE5>3.0.CO;2-1.
Receptor binding and gene expression of several members of the IGF gene family were examined in the rat brain following lesion of the hippocampal dentate gyrus granular cells by intradentate colchicine injection. Dentate granular cell loss was accompanied by extensive reactive gliosis in the lesioned hippocampus and damaged overlying cortex, as verified by the increase in GFAP mRNA and BS-1 lectin binding. At 4 days post-lesion, 125I-IGF-2 binding was dramatically increased within the lesioned dentate gyrus and damaged overlying cortex, and corresponded temporally and anatomically with increased IGF-BP2 gene expression following the lesion. Increased IGF-BP3 gene expression was only observed in the overlying cortex at 10 days post-lesion, and corresponded with an increase in 125I-IGF-1 binding at the injured surface of the cortex. Type-2 IGF receptor mRNA expression was reduced to background levels in the lesioned dentate gyrus, suggesting that IGF-BP2 was a major component of the observed increase in 125I-IGF-2 binding. In situ hybridization also revealed a prominent increase in IGF-1 mRNA expression by 4 days post-lesion, which was localized within the lesioned dentate gyrus and damaged cortical areas, and was shown to be expressed by microglia. While no IGF-2 mRNA expression was observed within the CNS, either prior to, or following the lesion, IGF-2 mRNA expression was observed in the choroid plexus, meningeal membranes, and in blood vessel endothelium, providing a potential source for the transport of IGF-2 into the CNS. In the injured CNS, increased IGF-BP2 expression may act to maintain or transport IGF-1 or IGF-2, as well as modulate the local autocrine and paracrine actions of the IGFs. Increased microglial IGF-1 expression following colchicine treatment correlates with the timing of a number of post-traumatic events within the CNS, suggesting that IGF-1 may have a role as a neuroprotectant for surviving neurons and signal for local neuronal sprouting, as well as a role in reactive astrogliosis.
通过齿状体内注射秋水仙碱损伤大鼠脑海马齿状回颗粒细胞后，检测了IGF基因家族几个成员的受体结合和基因表达情况。齿状颗粒细胞丢失伴随着损伤海马体和受损的上层皮质中广泛的反应性胶质增生，这通过GFAP mRNA和BS-1凝集素结合的增加得到证实。损伤后4天，损伤的齿状回和受损的上层皮质内125I-IGF-2结合显著增加，并且在时间和解剖学上与损伤后IGF-BP2基因表达增加相对应。仅在损伤后10天在上层皮质中观察到IGF-BP3基因表达增加，并且与皮质损伤表面处125I-IGF-1结合增加相对应。2型IGF受体mRNA表达在损伤的齿状回中降至背景水平，表明IGF-BP2是观察到的125I-IGF-2结合增加的主要成分。原位杂交还显示损伤后4天IGF-1 mRNA表达显著增加，其定位于损伤的齿状回和受损的皮质区域，并显示由小胶质细胞表达。虽然在损伤之前或之后在中枢神经系统内均未观察到IGF-2 mRNA表达，但在脉络丛、脑膜和血管内皮中观察到IGF-2 mRNA表达，这为IGF-2转运到中枢神经系统提供了潜在来源。在受损中枢神经系统中，IGF-BP2表达增加可能起到维持或转运IGF-1或IGF-2的作用，以及调节IGF的局部自分泌和旁分泌作用。秋水仙碱处理后小胶质细胞IGF-1表达增加与中枢神经系统内许多创伤后事件的时间相关，表明IGF-1可能作为存活神经元的神经保护剂和局部神经元发芽的信号，以及在反应性星形胶质增生中发挥作用。
