Ramos-Moreno Tania, Galazo Maria J, Porrero Cesar, Martínez-Cerdeño Verónica, Clascá Francisco
Department of Anatomy and Neuroscience, School of Medicine, Autónoma University, Ave. Arzobispo Morcillo s/n., Madrid 28029, Spain.
Eur J Neurosci. 2006 Jan;23(2):401-22. doi: 10.1111/j.1460-9568.2005.04567.x.
Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron populations in the developing and adult rodent brain. Secreted Reelin triggers a complex signaling pathway by binding lipoprotein and integrin membrane receptors in target cells. Reelin signaling regulates migration and dendritic growth in developing neurons, while it can modulate synaptic plasticity in adult neurons. To identify which adult neural circuits can be modulated by Reelin-mediated signaling, we systematically mapped the distribution of Reelin in adult rat brain using sensitive immunolabeling techniques. Results show that the distribution of intracellular and secreted Reelin is both very widespread and specific. Some interneuron and projection neuron populations in the cerebral cortex contain Reelin. Numerous striatal neurons are weakly immunoreactive for Reelin and these cells are preferentially located in striosomes. Some thalamic nuclei contain Reelin-immunoreactive cells. Double-immunolabeling for GABA and Reelin reveals that the Reelin-immunoreactive cells in the visual thalamus are the intrinsic thalamic interneurons. High local concentrations of extracellular Reelin selectively outline several dendrite spine-rich neuropils. Together with previous mRNA data, our observations suggest abundant axoplasmic transport and secretion in pathways such as the retino-collicular tract, the entorhino-hippocampal ('perforant') path, the lateral olfactory tract or the parallel fiber system of the cerebellum. A preferential secretion of Reelin in these neuropils is consistent with reports of rapid, activity-induced structural changes in adult brain circuits.
Reelin是一种大型细胞外基质糖蛋白，由发育中和成年啮齿动物大脑中的多个神经元群体分泌。分泌的Reelin通过与靶细胞中的脂蛋白和整合素膜受体结合来触发复杂的信号通路。Reelin信号通路调节发育中神经元的迁移和树突生长，同时它可以调节成年神经元的突触可塑性。为了确定哪些成年神经回路可以被Reelin介导的信号通路调节，我们使用敏感的免疫标记技术系统地绘制了成年大鼠大脑中Reelin的分布。结果表明，细胞内和分泌型Reelin的分布既非常广泛又具有特异性。大脑皮层中的一些中间神经元和投射神经元群体含有Reelin。许多纹状体神经元对Reelin的免疫反应较弱，这些细胞优先位于纹状体小体中。一些丘脑核含有Reelin免疫反应性细胞。对GABA和Reelin进行双重免疫标记显示，视觉丘脑中的Reelin免疫反应性细胞是丘脑固有中间神经元。细胞外Reelin的高局部浓度选择性地勾勒出几个富含树突棘的神经纤维网。结合先前的mRNA数据，我们的观察结果表明，在视网膜-丘脑束、内嗅-海马（“穿通”）通路、外侧嗅束或小脑的平行纤维系统等通路中存在丰富的轴浆运输和分泌。Reelin在这些神经纤维网中的优先分泌与成年大脑回路中快速的、活动诱导的结构变化的报道一致。
