Muramatsu Dai, Sato Yuki, Hishiyama Sohei, Miyamoto Yusei, Hisatsune Tatsuhiro
Department of Integrated Biosciences, University of Tokyo, Bioscience Building 402, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
Exp Neurol. 2005 Jul;194(1):1-11. doi: 10.1016/j.expneurol.2005.01.025.
GABAergic neurons in the neocortex contribute to various brain functions by regulating cortical pyramidal neurons. A deficiency of GABAergic neurons in the neocortex leads to the dysregulation of cortical neuronal circuits, but this can be overcome by cell transplantation, which provides a practical approach to repair damaged neuronal circuits. Here, we focused on the transplantation of committed neuronal progenitor cells. Because neuronal differentiation is considerably suppressed in the adult neocortex, we transfected proneural bHLH transcription factors into neural precursor cells to commit them to a neuronal lineage prior to the cell transplantation. We show that ventral neural stem cells transfected with Ngn1 are integrated as GABAergic neurons within a few days of transplantation into the adult mouse neocortex. These results demonstrate that the transplantation of committed neuronal progenitor cells is an effective method for brain repair.
新皮层中的γ-氨基丁酸能神经元通过调节皮层锥体神经元来参与多种脑功能。新皮层中γ-氨基丁酸能神经元的缺乏会导致皮层神经元回路失调，但这可以通过细胞移植来克服，细胞移植为修复受损神经元回路提供了一种切实可行的方法。在此，我们重点研究了定向神经元祖细胞的移植。由于成年新皮层中神经元分化受到显著抑制，我们在细胞移植前将神经源性bHLH转录因子转染到神经前体细胞中，使其定向分化为神经元谱系。我们发现，用Neurogenin 1（Ngn1）转染的腹侧神经干细胞在移植到成年小鼠新皮层后的几天内就整合为γ-氨基丁酸能神经元。这些结果表明，定向神经元祖细胞的移植是一种有效的脑修复方法。
