The development of peripheral cold neural circuits based on TRPM8 expression.
The development of peripheral cold neural circuits based on TRPM8 expression.
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DOI：
10.1016/j.neuroscience.2010.05.039
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发表时间：
2010-08-25
期刊：
影响因子：
3.3
通讯作者：
McKemy, D. D.
中科院分区：
文献类型：
--
作者：
Takashima, Y.;Ma, L.;McKemy, D. D.
躯体感觉系统的传入神经纤维是一个分子多样性的细胞群，它检测各种各样的环境刺激，并最终将这些外部线索转化为感觉感受器。传入介导的热刺激检测表达TRP家族的温度敏感性离子通道的库，其赋予这些神经对环境中的温度的宽度作出响应的能力。冷和薄荷醇受体TRPM8负责检测冷，与其他热传感器不同，它可以检测无害和有害的温度。这种单一分子如何执行如此多样化的功能目前尚不清楚，但成人组织中的表达分析表明，TRPM 8神经元是一个分子多样性群体，这种多样性可能是差异功能的基础。为了确定这种表型是如何建立的，我们研究了TRPM8表达的发育时间过程中使用的小鼠转基因系，其中GFP表达是由TRPM8转录启动子（Trpm8GFP）驱动。我们发现Trpm8GFP的表达开始于胚胎第15.5天（E15.5）之前，之后表达达到在成年神经元中观察到的水平。到E18.5，Trpm8GFP神经元的中央轴突到达脊髓背角，但神经活动的解剖定位和体内测量表明，直到出生后第一周才建立起功能齐全的冷回路。此外，Trpm8GFP神经元经历神经化学表型的转变，最终在出生后第14天达到标记物如TRPV1、CGRP、外周蛋白和NF 200的成人表达。因此，基于免疫化学，解剖和功能的标准，活跃的冷神经回路完全建立的第二周出生后，从而表明，重要的外在或内在的机制是积极的，在此之前的发展阶段。
Afferent nerve fibers of the somatosensory system are a molecularly diverse cell population that detects a varied range of environmental stimuli, converting these external cues ultimately into a sensory percept. Afferents mediating detection of thermal stimuli express a repertoire of temperature sensitive ion channels of the TRP family which endow these nerves with the ability to respond to the breadth of temperatures in the environment. The cold and menthol receptor TRPM8 is responsible for detection of cold and, unlike other thermosensors, detects both innocuous and noxious temperatures. How this single molecule can perform such diverse functions is currently unknown, but expression analyses in adult tissues shows that TRPM8 neurons are a molecularly diverse population and it is likely that this diversity underlies differential functionality. To determine how this phenotype is established, we examined the developmental time course of TRPM8 expression using a mouse transgenic line in which GFP expression is driven by the TRPM8 transcriptional promoter (Trpm8GFP). We find that Trpm8GFP expression begins prior to embryonic day 15.5 (E15.5) after which expression reaches levels observed in adult neurons. By E18.5, central axons of Trpm8GFP neurons reach the spinal cord dorsal horn, but anatomical localization and in vivo measurements of neural activity suggest that fully functional cold circuits are not established until after the first postnatal week. Additionally, Trpm8GFP neurons undergo a transition in neurochemical phenotype, ultimately reaching adult expression of markers such TRPV1, CGRP, peripherin, and NF200 by postnatal day 14. Thus, based on immunochemical, anatomical and functional criteria, active cold neural circuits are fully established by the second week postnatal, thereby suggesting that important extrinsic or intrinsic mechanisms are active prior to this developmental stage.
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影响因子：
5.5
作者：
Baccei, ML;Bardoni, R;Fitzgerald, M
通讯作者：
Fitzgerald, M
影响因子：
5.5
作者：
LAWSON, SN;WADDELL, PJ
通讯作者：
WADDELL, PJ
影响因子：
16.2
作者：
Colburn, Raymond W.;Lubin, Mary Lou;Qin, Ning
通讯作者：
Qin, Ning
影响因子：
5.3
作者：
Dhaka, Ajay;Earley, Taryn J.;Patapoutian, Ardem
通讯作者：
Patapoutian, Ardem
DOI：
10.1007/bf01236122
发表时间：
1979-01-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
LAWSON, SN;BISCOE, TJ
通讯作者：
BISCOE, TJ