Experience-dependent regulation of TrkB isoforms in rodent visual cortex.

Experience-dependent regulation of TrkB isoforms in rodent visual cortex.
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DOI:
10.1002/dneu.20701
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发表时间:
2009-04
影响因子:
3
通讯作者:
Turrigiano, Gina G.
Turrigiano, Gina G.
中科院分区:
医学3区
文献类型:
--
作者:
Bracken, Bethany K.;Turrigiano, Gina G.

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在初级视皮层(V1)内,BDNF通过其高亲和力受体TrkB信号传导对于正常发育和经验依赖性可塑性非常重要。TrkB以几种可变剪接的同种型表达,包括全长TrkB(TrkB.FL)和几种缺乏细胞内酪氨酸激酶结构域的截短同种型(TrkB. T1、TrkB. T2和TrkB. T4)。这些异构体是BDNF信号传导的重要组成部分,但对其表达的发育或经验依赖性调控知之甚少。免疫组化结果显示,TrkB.FL和TrkB. T1在V1区的中间神经元和锥体神经元中表达,而在皮质星形胶质细胞中不表达。我们使用实时PCR定量BDNF的mRNA表达的变化,四个TrkB亚型,和低亲和力受体P75 NTR在正常发育过程中,并在两个不同年龄的视觉剥夺。BDNF的表达在出生后10天(P10)和P30之间增加,并且在前临界期(P14-P17)和临界期(P18-P21)被3天的视觉剥夺迅速下调。在相同的发育时期,每个TrkB亚型的表达是独立调节的; TrkB.T1增加,TrkB.FL和TrkB.T2减少,TrkB.T4表现出短暂的变化。无论是短暂的视觉剥夺,也没有长期的黑暗饲养诱导的变化TrkB.FL或TrkB. T1表达。短暂的视觉剥夺可降低TrkB. T4的表达,而长时间的暗饲养可上调TrkB. T4、TrkB. T2和P75 NTR的表达。我们的数据表明,TrkB异构体的表达可以选择性地调节视觉经验,并可能有助于经验依赖性皮层可塑性。
Within primary visual cortex (V1), BDNF signaling through its high affinity receptor TrkB is important for normal development and experience-dependent plasticity. TrkB is expressed in several alternatively spliced isoforms, including full length TrkB (TrkB.FL), and several truncated isoforms (TrkB.T1, TrkB.T2 and TrkB.T4) that lack the intracellular tyrosine kinase domain. These isoforms are important components of BDNF signaling, yet little is known about the developmental or experience-dependent regulation of their expression. Using immunohistochemistry, we found TrkB.FL and TrkB.T1 expressed in interneurons and pyramidal neurons within V1, but not in cortical astrocytes. We used real-time PCR to quantify changes in mRNA expression of BDNF, the four TrkB isoforms, and the low affinity receptor P75NTR during normal development, and in response to visual deprivation at two different ages. BDNF expression increased between postnatal days 10 (P10) and P30, and was rapidly down-regulated by 3 days of visual deprivation during both the pre-critical period (P14–P17) and the critical period (P18–P21). Over the same developmental period expression of each TrkB isoform was regulated independently; TrkB.T1 increased, TrkB.FL and TrkB.T2 decreased, and TrkB.T4 showed transient changes. Neither brief visual deprivation nor prolonged dark-rearing induced changes in TrkB.FL or TrkB.T1 expression. However, TrkB.T4 expression was reduced by brief visual deprivation, while TrkB.T4, TrkB.T2 and P75NTR were up-regulated by prolonged dark-rearing into the critical period. Our data indicate that TrkB isoform expression can be selectively regulated by visual experience, and may contribute to experience-dependent cortical plasticity.
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