F. Hoffmann-La Roche AG, Pharma Research & Early Development, DTA Neuroscience, Basel, Switzerland.
PLoS One. 2013 May 14;8(5):e59269. doi: 10.1371/journal.pone.0059269. Print 2013.
Here, we have developed a highly sensitive immunoassay for Dcx to characterize expression in brain and cerebrospinal fluid (CSF) of rodents. We demonstrate that Dcx is widely expressed during development in various brain regions and as well can be detected in cerebrospinal fluid of rats (up to 30 days postnatal). While Dcx protein level decline in adulthood and were detectable in neurogenic regions of the adult rodent brain, similar levels were also detectable in brain regions expected to bear no neurogenesis including the cerebral cortex and CA1/CA3 enriched hippocampus. We monitored DCX protein levels after paradigms to increase or severely decrease adult hippocampal neurogenesis, namely physical activity and cranial radiation, respectively. In both paradigms, Dcx protein- and mRNA-levels clearly reflected changes in neurogenesis in the hippocampus. However, basal Dcx-levels are unaffected in non-neurogenic regions (e.g. CA1/CA3 enriched hippocampus, cortex). These data suggest that there is a substantial "non-neurogenic" pool of Dcx- protein, whose regulation can be uncoupled from adult neurogenesis suggesting caution for the interpretation of such studies.
在这里,我们开发了一种高度敏感的 Dcx 免疫分析法,用于描述啮齿动物大脑和脑脊液(CSF)中的表达。我们证明 Dcx 在发育过程中在各种大脑区域广泛表达,并且在大鼠的脑脊液中也可以检测到(出生后 30 天内)。虽然 Dcx 蛋白水平在成年期下降,并且在成年啮齿动物的神经发生区域中可检测到,但在预计不具有神经发生的脑区(包括大脑皮层和富含 CA1/CA3 的海马体)中也可以检测到类似水平。我们监测了增加或严重减少成年海马体神经发生的范式(即体力活动和颅辐射)后 DCX 蛋白水平。在这两种范式中,Dcx 蛋白和 mRNA 水平都清楚地反映了海马体神经发生的变化。然而,在非神经发生区域(例如富含 CA1/CA3 的海马体、皮层)中,基础 Dcx 水平不受影响。这些数据表明存在大量的“非神经发生”Dcx 蛋白池,其调节可以与成年神经发生解耦,这表明在解释此类研究时需要谨慎。