Marichal Nicolás, García Gabriela, Radmilovich Milka, Trujillo-Cenóz Omar, Russo Raúl E
Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
J Neurosci. 2009 Aug 12;29(32):10010-24. doi: 10.1523/JNEUROSCI.6183-08.2009.
The region that surrounds the central canal of the spinal cord derives from the neural tube and retains a substantial degree of plasticity. In turtles, this region is a neurogenic niche where newborn neurons coexist with precursors, a fact that may be related with the endogenous repair capabilities of low vertebrates. Immunohistochemical evidence suggests that the ependyma of the mammalian spinal cord may contain cells with similar properties, but their actual nature remains unsolved. Here, we combined immunohistochemistry for cell-specific markers with patch-clamp recordings to test the hypothesis that the ependyma of neonatal rats contains immature neurons similar to those in low vertebrates. We found that a subclass of cells expressed HuC/D neuronal proteins, doublecortin, and PSA-NCAM (polysialylated neural cell adhesion molecule) but did not express NeuN (anti-neuronal nuclei). These immature neurons displayed electrophysiological properties ranging from slow Ca(2+)-mediated responses to fast repetitive Na(+) spikes, suggesting different stages of maturation. These cells originated in the embryo, because we found colocalization of neuronal markers with 5-bromo-2'-deoxyuridine when injected during embryonic day 7-17 but not in postnatal day 0-5. Our findings represent the first evidence that the ependyma of the rat spinal cord contains cells with molecular and functional features similar to immature neurons in adult neurogenic niches. The fact that these cells retain the expression of molecules that participate in migration and neuronal differentiation raises the possibility that the ependyma of the rat spinal cord is a reservoir of immature neurons in "standby mode," which under some circumstances (e.g., injury) may complete their maturation to integrate spinal circuits.
围绕脊髓中央管的区域起源于神经管，并保留了相当程度的可塑性。在龟类中，该区域是一个神经发生微环境，新生神经元与前体细胞共存，这一事实可能与低等脊椎动物的内源性修复能力有关。免疫组织化学证据表明，哺乳动物脊髓的室管膜可能含有具有类似特性的细胞，但其实际性质仍未明确。在这里，我们将针对细胞特异性标志物的免疫组织化学与膜片钳记录相结合，以检验新生大鼠室管膜含有与低等脊椎动物中相似的未成熟神经元这一假说。我们发现，一类细胞表达HuC/D神经元蛋白、双皮质素和多唾液酸神经细胞黏附分子（PSA-NCAM），但不表达NeuN（抗神经元细胞核）。这些未成熟神经元表现出从缓慢的钙介导反应到快速重复钠峰的电生理特性，表明处于不同的成熟阶段。这些细胞起源于胚胎期，因为我们在胚胎第7至17天注射5-溴-2'-脱氧尿苷时发现神经元标志物与之共定位，而在出生后第0至5天则未发现。我们的研究结果首次证明，大鼠脊髓室管膜含有在分子和功能特征上与成年神经发生微环境中的未成熟神经元相似的细胞。这些细胞保留参与迁移和神经元分化的分子表达这一事实，增加了大鼠脊髓室管膜是处于“备用模式”的未成熟神经元储备库的可能性，在某些情况下（如损伤），这些神经元可能完成成熟以整合到脊髓回路中。
