Alcántara S, Frisén J, del Río J A, Soriano E, Barbacid M, Silos-Santiago I
Department of Cell Biology, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain.
J Neurosci. 1997 May 15;17(10):3623-33. doi: 10.1523/JNEUROSCI.17-10-03623.1997.
Newborn mice carrying targeted mutations in genes encoding neurotrophins or their signaling Trk receptors display severe neuronal deficits in the peripheral nervous system but not in the CNS. In this study, we show that trkB (-/-) mice have a significant increase in apoptotic cell death in different regions of the brain during early postnatal life. The most affected region in the brain is the dentate gyrus of the hippocampus, although elevated levels of pyknotic nuclei were also detected in cortical layers II and III and V and VI, the striatum, and the thalamus. Furthermore, axotomized hippocampal and motor neurons of trkB (-/-) mice have significantly lower survival rates than those of wild-type littermates. These results suggest that neurotrophin signaling through TrkB receptors plays a role in the survival of CNS neurons during postnatal development. Moreover, they indicate that TrkB receptor signaling protects subpopulations of CNS neurons from injury- and axotomy-induced cell death.
携带编码神经营养因子或其信号转导Trk受体基因靶向突变的新生小鼠，在外周神经系统中表现出严重的神经元缺陷，但在中枢神经系统中却没有。在本研究中，我们发现TrkB（-/-）小鼠在出生后早期，大脑不同区域的凋亡细胞死亡显著增加。大脑中受影响最严重的区域是海马齿状回，不过在皮质层II、III、V和VI、纹状体以及丘脑中也检测到了固缩核水平升高。此外，TrkB（-/-）小鼠的海马和运动神经元在轴突切断后，其存活率显著低于野生型同窝小鼠。这些结果表明，通过TrkB受体的神经营养因子信号传导在出生后发育过程中对中枢神经系统神经元的存活起作用。而且，它们表明TrkB受体信号传导可保护中枢神经系统神经元亚群免受损伤和轴突切断诱导的细胞死亡。
