Smedfors Gabriella, Olson Lars, Karlsson Tobias E
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Front Mol Neurosci. 2018 Feb 19;11:42. doi: 10.3389/fnmol.2018.00042. eCollection 2018.
An appropriate strength of Nogo-like signaling is important to maintain synaptic homeostasis in the CNS. Disturbances have been associated with schizophrenia, MS and other diseases. Blocking Nogo-like signaling may improve recovery after spinal cord injury, stroke and traumatic brain injury. To understand the interacting roles of an increasing number of ligands, receptors and modulators engaged in Nogo-like signaling, the transcriptional activity of these genes in the same brain areas from birth to old age in the normal brain is needed. Thus, we have quantitatively mapped the innate expression of 11 important genes engaged in Nogo-like signaling. Using hybridization, we located and measured the amount of mRNA encoding Nogo-A, OMgp, NgR1, NgR2, NgR3, Lingo-1, Troy, Olfactomedin, LgI1, ADAM22, and MAG, in 18 different brain areas at six different ages (P0, 1, 2, 4, 14, and 104 weeks). We show gene- and area-specific activities and how the genes undergo dynamic regulation during postnatal development and become stable during adulthood. Hippocampal areas underwent the largest changes over time. We only found differences between individual cortical areas in Troy and MAG. Subcortical areas presented the largest inter-regional differences; lateral and basolateral amygdala had markedly higher expression than other subcortical areas. The widespread differences and unique expression patterns of the different genes involved in Nogo-like signaling suggest that the functional complexes could look vastly different in different areas.
适当强度的类Nogo信号对于维持中枢神经系统的突触稳态至关重要。信号紊乱与精神分裂症、多发性硬化症和其他疾病有关。阻断类Nogo信号可能会改善脊髓损伤、中风和创伤性脑损伤后的恢复情况。为了解参与类Nogo信号的配体、受体和调节剂数量不断增加所起的相互作用,需要了解这些基因在正常大脑从出生到老年的相同脑区中的转录活性。因此,我们定量绘制了参与类Nogo信号的11个重要基因的固有表达图谱。通过杂交,我们定位并测量了在六个不同年龄(出生后0、1、2、4、14和104周)的18个不同脑区中编码Nogo-A、OMgp、NgR1、NgR2、NgR3、Lingo-1、Troy、嗅觉介质、LgI1、ADAM22和MAG的mRNA量。我们展示了基因和区域特异性活性,以及这些基因在出生后发育过程中如何经历动态调节并在成年期变得稳定。海马区随时间变化的幅度最大。我们仅在Troy和MAG基因中发现了不同皮质区域之间的差异。皮质下区域呈现出最大的区域间差异;外侧和基底外侧杏仁核的表达明显高于其他皮质下区域。参与类Nogo信号的不同基因广泛存在的差异和独特的表达模式表明,不同区域的功能复合物可能存在很大差异。