Heuer H, Christ S, Friedrichsen S, Brauer D, Winckler M, Bauer K, Raivich G
Max-Planck Institute for Experimental Endocrinology, Feodor-Lynen-Str. 7, D-30625 Hannover, Germany.
Neuroscience. 2003;119(1):43-52. doi: 10.1016/s0306-4522(03)00100-3.
Connective tissue growth factor (CTGF) belongs to a family of secreted, extracellular matrix-associated proteins that are involved in the regulation of cellular functions such as adhesion, migration, mitogenesis, differentiation and survival. Recent studies have also suggested the up-regulation of CTGF in response to trauma, scar formation and excitotoxicity in the CNS. To further elucidate the localization and regulation of this molecule in the rat brain we performed in situ hybridization experiments and found a very strong and selective expression of CTGF messenger ribonucleic acid (mRNA) on the band of layer VII neurons throughout the adult cerebral cortex. Similarly strong neuronal expression was also present in the dorsal endopiriform nucleus, extending rostrally from the ventrocaudal cortical layer VII, and in the deep layers of the olfactory glomeruli and the accessory olfactory nucleus. Double in situ hybridization confirmed selective CTGF mRNA expression on a subpopulation (approximately 35%) of microtubule-associated protein 2 mRNA-positive neurons in the cortical layer VII and the dorsal endopiriform nucleus. The nucleus of lateral olfactory tract showed moderate signal intensity; other parts of the forebrain, mesencephalon and brain stem only revealed a very weak level of CTGF mRNA expression. Non-neuronal expression was rare, considerably weaker than on cortical layer VII neurons, and normally associated with blood vessels. Developmental analysis of CTGF mRNA expression in embryonic and postnatal mouse also showed a moderately late onset at embryonic day 16-18, and confirmed the presence of CTGF mRNA in cortical layer VII in a second rodent species. Interestingly, injury experiments using direct cerebral trauma or injection of excitotoxic kainic acid into rat brain failed to up-regulate CTGF mRNA after injury and during the ensuing period of neuronal cell death, gliosis and neural scar tissue formation. Altogether, the current data suggest a constitutive role of CTGF, particularly in the adult cerebral cortex. In view of the strong ascending projections of subplate neurons into cortical layer 1, this molecule may be involved in the modulation of synaptic input to apical dendrites of pyramidal neurons.
结缔组织生长因子（CTGF）属于一类分泌型细胞外基质相关蛋白家族，参与调节细胞功能，如黏附、迁移、有丝分裂、分化和存活。最近的研究还表明，在中枢神经系统中，CTGF会因创伤、瘢痕形成和兴奋性毒性而表达上调。为了进一步阐明该分子在大鼠脑中的定位和调控，我们进行了原位杂交实验，发现在整个成年大脑皮质的VII层神经元带中，CTGF信使核糖核酸（mRNA）有非常强烈且选择性的表达。同样强烈的神经元表达也出现在背侧梨状内嗅核，从腹尾侧皮质VII层向前延伸，以及嗅小球深层和副嗅核中。双重原位杂交证实，在皮质VII层和背侧梨状内嗅核中，微管相关蛋白2 mRNA阳性神经元的一个亚群（约35%）上有选择性的CTGF mRNA表达。外侧嗅束核显示出中等信号强度；前脑、中脑和脑干的其他部分仅显示出非常弱的CTGF mRNA表达水平。非神经元表达很少见，比皮质VII层神经元上的表达弱得多，且通常与血管相关。对胚胎期和出生后小鼠CTGF mRNA表达的发育分析也显示，在胚胎第16 - 18天有适度的延迟出现，并证实了在第二种啮齿动物物种的皮质VII层中存在CTGF mRNA。有趣的是，使用直接脑外伤或向大鼠脑内注射兴奋性毒性的 kainic 酸进行的损伤实验未能在损伤后以及随后的神经元细胞死亡、胶质增生和神经瘢痕组织形成期间上调CTGF mRNA。总之，目前的数据表明CTGF具有组成性作用，特别是在成年大脑皮质中。鉴于板下层神经元向皮质第1层有强烈的上行投射，该分子可能参与调节对锥体神经元顶树突的突触输入。
