Birey Fikri, Aguirre Adan
Graduate Program in Genetics and Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York 11794.
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York 11794
J Neurosci. 2015 Apr 29;35(17):6946-51. doi: 10.1523/JNEUROSCI.0356-15.2015.
Neuron-glial antigen 2-positive (NG2(+)) glial cells are the most proliferative glia type in the adult CNS, and their tile-like arrangement in adult gray matter is under tight regulation. However, little is known about the cues that govern this unique distribution. To this end, using a NG2(+) glial cell ablation model in mice, we examined the repopulation dynamics of NG2(+) glial cells in the mature and aged mice gray matter. We found that some resident NG2(+) glial cells that escaped depletion rapidly enter the cell cycle to repopulate the cortex with altered spatial distribution. We reveal that netrin-1 signaling is involved in the NG2(+) glial cell early proliferative, late repopulation, and distribution response after ablation in the gray matter. However, ablation of NG2(+) glial cell in older animals failed to stimulate a similar repopulation response, possibly because of a decrease in the sensitivity to netrin-1. Our findings indicate that endogenous netrin-1 plays a role in NG2(+) glial cell homeostasis that is distinct from its role in myelination.
神经元胶质抗原2阳性（NG2(+)）胶质细胞是成年中枢神经系统中增殖能力最强的胶质细胞类型，它们在成年灰质中的瓦片样排列受到严格调控。然而，对于控制这种独特分布的线索却知之甚少。为此，我们利用小鼠NG2(+)胶质细胞消融模型，研究了成熟和老龄小鼠灰质中NG2(+)胶质细胞的重新填充动态。我们发现，一些未被耗尽的驻留NG2(+)胶质细胞会迅速进入细胞周期，以改变的空间分布重新填充皮质。我们揭示，netrin-1信号通路参与了灰质中NG2(+)胶质细胞消融后的早期增殖、后期重新填充及分布反应。然而，在老龄动物中消融NG2(+)胶质细胞未能刺激类似的重新填充反应，这可能是由于对netrin-1的敏感性降低所致。我们的研究结果表明，内源性netrin-1在NG2(+)胶质细胞稳态中发挥作用，这与其在髓鞘形成中的作用不同。
