Gao Xiang, Smith George M, Chen Jinhui
Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY 40536, USA.
Exp Neurol. 2009 Jan;215(1):178-90. doi: 10.1016/j.expneurol.2008.10.009. Epub 2008 Oct 30.
Neurons are continuously added to the hippocampal dentate gyrus throughout life. These neurons must develop dendritic arbors and spines by which they form synapses for making functional connections with existing neurons. The molecular mechanisms that regulate dendritic development and synaptic formation of postnatal-born granular neurons in the dentate gyrus are largely unknown. Hippocampal dentate gyrus (HDG) has been shown to express high level of brain-derived neurotrophic factor (BDNF). Here we reported that when BDNF is conditionally knockout in the postnatal-born granular neurons of the HDG, the mutant neurons exhibit aberrant morphological development with less dendritic branches, shorter dendritic length, and lower density of dendritic spines, while their primary dendrites are not obviously affected. Even though, these BDNF-deficient granular neurons develop immature dendritic spines to initiate synaptic contacts with afferent axons, they fail to develop or maintain mature spine structures. Thus, these postnatal-born neurons have fewer numbers of synapses, particularly mature synaptic spines. These results suggest that BDNF plays an important role during dendritic development, synaptic formation and synaptic maturation in postnatal-born granular neurons of the HDG in vivo.
神经元在整个生命过程中持续添加到海马齿状回。这些神经元必须发育出树突分支和棘突，通过它们形成突触，以便与现有神经元建立功能连接。调节齿状回中出生后颗粒神经元树突发育和突触形成的分子机制在很大程度上尚不清楚。海马齿状回（HDG）已被证明表达高水平的脑源性神经营养因子（BDNF）。在此我们报告，当BDNF在HDG出生后颗粒神经元中条件性敲除时，突变神经元表现出异常的形态发育，树突分支减少、树突长度缩短以及树突棘密度降低，而它们的初级树突没有明显受到影响。即便如此，这些缺乏BDNF的颗粒神经元发育出不成熟的树突棘以启动与传入轴突的突触接触，但它们无法发育或维持成熟的棘突结构。因此，这些出生后神经元的突触数量较少，尤其是成熟的突触棘。这些结果表明，BDNF在体内HDG出生后颗粒神经元的树突发育、突触形成和突触成熟过程中发挥重要作用。
