Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA.
Department of Pharmacology, Physiology and Neuroscience, Rutgers-NJMS, Newark, New Jersey, USA.
Glia. 2023 Oct;71(10):2383-2400. doi: 10.1002/glia.24430. Epub 2023 Jun 19.
The precise timing of neural progenitor development and the correct balance between proliferation and differentiation are crucial to generating a functional brain. The number, survival, and differentiation of neural progenitors during postnatal neurogenesis and gliogenesis is a highly regulated process. Postnatally, the majority of brain oligodendrocytes are generated from progenitors residing in the subventricular zone (SVZ), the germinal niche surrounding the lateral ventricles. In this study, we demonstrate that the p75 neurotrophin receptor (p75NTR) is highly expressed by OPCs in the postnatal male and female rat SVZ. Whereas the p75NTR is known to initiate apoptotic signaling after brain injury, it is highly expressed by proliferating progenitors in the SVZ, suggesting that it may have a different function during development. Lack of p75NTR reduced progenitor proliferation and caused premature oligodendrocyte differentiation and maturation both in vitro and in vivo, leading to aberrant early myelin formation. Our data reveal a novel role for p75NTR as a rheostat for oligodendrocyte production and maturation during myelin formation in the postnatal rat brain.
神经祖细胞发育的精确时间和增殖与分化之间的正确平衡对于产生功能正常的大脑至关重要。在出生后的神经发生和神经胶质发生过程中，神经祖细胞的数量、存活和分化是一个高度受调控的过程。在出生后，大多数脑少突胶质细胞是由位于侧脑室周围的脑室下区（SVZ）中的祖细胞产生的。在这项研究中，我们证明 p75 神经营养因子受体（p75NTR）在雄性和雌性新生大鼠 SVZ 中的 OPCs 中高度表达。虽然 p75NTR 已知在脑损伤后会引发凋亡信号，但它在 SVZ 中的增殖祖细胞中高度表达，表明它在发育过程中可能具有不同的功能。缺乏 p75NTR 会减少祖细胞的增殖，并导致体外和体内少突胶质细胞过早分化和成熟，导致早期髓鞘形成异常。我们的数据揭示了 p75NTR 在新生大鼠大脑中髓鞘形成过程中作为少突胶质细胞产生和成熟的变阻器的新作用。
