Cash-Padgett Tyler, Sawa Akira, Jaaro-Peled Hanna
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
Neurosci Res. 2016 Apr;105:75-9. doi: 10.1016/j.neures.2015.10.001. Epub 2015 Oct 13.
Chemokines play important roles in the central nervous system, including mediating neuroinflammation and guiding the intracortical migration of interneurons during development. Alteration in parvalbumin-positive interneurons is a key neuropathological hallmark of multiple mental conditions. We recently reported a significant reduction in the expression of CXCL12 in olfactory neurons from sporadic cases with schizophrenia compared with matched controls, suggesting a role for CXCR4/CXCL12 signaling in mental conditions. Thus, we depleted the chemokine receptor Cxcr4 from mice using the parvalbumin-2A-Cre line. The conditional knockout mice exhibited a unique behavioral phenotype involving increased stereotypy. Stereotypy is observed in many psychiatric conditions, including schizophrenia, autism, and dementia. Thus, the Cxcr4 conditional knockout mice may serve as a model for this symptomatic feature.
趋化因子在中枢神经系统中发挥着重要作用,包括介导神经炎症以及在发育过程中引导中间神经元的皮质内迁移。小清蛋白阳性中间神经元的改变是多种精神疾病的关键神经病理学标志。我们最近报告称,与匹配的对照相比,散发性精神分裂症病例的嗅觉神经元中CXCL12的表达显著降低,这表明CXCR4/CXCL12信号传导在精神疾病中发挥作用。因此,我们使用小清蛋白-2A-Cre系从小鼠中耗尽趋化因子受体Cxcr4。条件性敲除小鼠表现出一种独特的行为表型,包括刻板行为增加。刻板行为在许多精神疾病中都有观察到,包括精神分裂症、自闭症和痴呆症。因此,Cxcr4条件性敲除小鼠可能作为这种症状特征的模型。