Developmental changes of TrkB signaling in response to exogenous brain-derived neurotrophic factor in primary cortical neurons.
Developmental changes of TrkB signaling in response to exogenous brain-derived neurotrophic factor in primary cortical neurons.
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DOI：
10.1111/j.1471-4159.2011.07528.x
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发表时间：
2011-12
影响因子：
4.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Zhou X;Xiao H;Wang H
新皮质回路在早期发育的关键时期对感觉体验最敏感。先前的研究表明 BDNF 和 GABA 能抑制可能控制关键期的时间。通过使用体外成熟模型，我们发现 DIV（体外天）7 的神经元，即功能性突触开始形成和 GABA 能抑制出现的时期，表现出外源 BDNF 对 ERK1/2 和 CREB 的最动态激活。 BDNF 刺激的 CREB 靶基因转录上调在 DIV 7 神经元中也是最高的。 ERK1/2和CREB活性的基础水平以及CREB靶基因的表达随着成熟而增加，并且DIV 13和22的神经元对BDNF表现出较少的动态反应。此外，我们发现发育调节的 GABA 能抑制与成熟过程中 BDNF 介导的信号传导的减弱相关。 BDNF 刺激以及 GABA 能抑制的抑制增强了成熟神经元中 ERK1/2-CREB 信号传导和基因转录的激活。相反，BDNF 刺激加上 GABA 能抑制的增强，降低了年轻神经元细胞内信号传导的总体诱导。我们认为，较不动态的分子变化可能在成熟过程中可塑性的丧失中发挥一定作用。
Neocortical circuits are most sensitive to sensory experience during a critical period of early development. Previous studies implicate that BDNF and GABAergic inhibition may control the timing of the critical period. By using an in vitro maturation model, we found that neurons at DIV (day in vitro) 7, around a period when functional synapses start to form and GABAergic inhibition emerges, displayed the most dynamic activation of ERK1/2 and CREB by exogenous BDNF. The BDNF-stimulated transcriptional up-regulation of CREB target genes was also the highest in DIV 7 neurons. The basal level of ERK1/2 and CREB activity, as well as the expression of CREB target genes, increased along with maturation, and neurons at DIV 13 and 22 displayed less dynamic responses to BDNF. Further, we found that the developmentally regulated GABAergic inhibition correlated with the decline of BDNF-mediated signaling during maturation. BDNF stimulation along with suppression of GABAergic inhibition enhanced the activation of ERK1/2-CREB signaling and gene transcription in mature neurons. Conversely, BDNF stimulation along with enhancement of GABAergic inhibition reduced the overall induction of intracellular signaling in younger neurons. We propose that the less dynamic molecular changes may play a certain role in the loss of plasticity during maturation.
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影响因子：
2.5
作者：
Ivanova, T;Beyer, C
通讯作者：
Beyer, C
影响因子：
64.8
作者：
CRAIR, MC;MALENKA, RC
通讯作者：
MALENKA, RC
DOI：
10.1016/0006-291x(91)90531-b
发表时间：
1991-01-15
影响因子：
3.1
作者：
KAISHO, Y;SHINTANI, A;IGARASHI, K
通讯作者：
IGARASHI, K
影响因子：
2.9
作者：
DICHTER, MA
通讯作者：
DICHTER, MA
影响因子：
2.9
作者：
Hogsden, Jennifer L.;Dringenberg, Hans C.
通讯作者：
Dringenberg, Hans C.