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Brainstem and spinal cord expression of novel and existing neuronal connexins determined using transgenic reporter mice.

使用转基因报告小鼠测定新型和现有神经元连接蛋白的脑干和脊髓表达。

基本信息

批准号：
BB/E001831/1
负责人：
Jim Deuchars
金额：
$ 43.87万
依托单位：
University of Leeds
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2007
资助国家：
英国
起止时间：
2007 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FE001831%2F1
关键词：
Brainstem spinal cord expression novel

项目摘要

The brain contains millions of nerve cells (neurones), generally organised into discrete collections to perform specific functions. These neurones communicate with selected partners to make such functions possible. Until recently the only way that brain cells were thought to communicate with one another was through chemical synapses where an electrical impulse in one neurone releases a chemical which diffuses across a small space to set up an electrical signal in another neurone. However, it has recently emerged that neurones can communicate by channels which allow two cells to be directly coupled / gap junctions. These gap junctions allow the passage of electrical signals and some other cellular metabolites directly between the cells. This direct connection permits fast transfer of information between the cells and allows groups of neurones to become synchronised in their electrical activity. Such synchrony is now seen as important for determining many brain functions. The gap junctions are made up of different proteins, some of which are a family called connexins. There are many connexins, but only two of these have been known to be present in neurones within the brain, Cx36 and Cx45. However, their distribution is not known in the brainstem and spinal cord, areas of the nervous system directly affecting breathing, blood pressure, heart rate, pain sensation and movement etc. In addition, our preliminary data shows that a new connexin, Cx30.2, is present in many neurones in these regions. We therefore propose to investigate the distribution of these connexins in the brainstem and spinal cord. Unfortunately, two conventional approaches to determining connexin distribution have proven unreliable, with many false answers. We will therefore base our studies on a new, validated approach where mice have been genetically altered to produce a marker within the cells that make each individual connexin. By a simple reaction we can see in tissue sections the cells where the connexins are made. Since the brainstem and spinal cord contain neurones with different functions we will work out which cell types express the particular connexins using additional anatomical and physiological methods. We will also cross breed mice with different types of markers to see if one cell can produce more than one connexin. This is important as the presence of different connexins in a single cell may influence how the particular gap junction works. These studies will therefore provide new data about the distribution, cell types and co-localisation of the neuronal connexins. Since our preliminary studies have suggested the presence of connexins in neuronal groups not previously known to express gap junctions, full analysis is likely to reveal novel populations for future studies. The identification of such neuronal groups with the capabilities of synchronising their activity will provide new areas of understanding of how these brain regions function.

大脑包含数百万个神经细胞（神经元），通常被组织成离散的集合来执行特定的功能。这些神经元与选定的伙伴进行通信，使这些功能成为可能。直到最近，人们还认为脑细胞之间的唯一交流方式是通过化学突触，即一个神经元中的电脉冲释放出一种化学物质，这种化学物质扩散到一个小空间中，在另一个神经元中产生电信号。然而，最近出现的是，神经元可以通过允许两个细胞直接偶联/间隙连接的通道进行通信。这些缝隙连接允许电信号和一些其他细胞代谢物直接在细胞之间通过。这种直接连接允许细胞之间的信息快速传递，并允许神经元组在其电活动中同步。这种同步性现在被视为决定许多大脑功能的重要因素。差距连接由不同的蛋白质组成，其中一些是称为连接蛋白的家族。有许多连接蛋白，但已知其中只有两种存在于脑内的神经元中，Cx 36和Cx45。然而，他们的分布是不知道在脑干和脊髓，区域的神经系统直接影响呼吸，血压，心率，痛觉和运动等，此外，我们的初步数据显示，一个新的连接蛋白，Cx30.2，是目前在许多神经元在这些地区。因此，我们建议调查这些连接蛋白在脑干和脊髓中的分布。不幸的是，两种传统的方法来确定连接蛋白分布已被证明是不可靠的，有许多错误的答案。因此，我们的研究将基于一种新的、经过验证的方法，即对小鼠进行基因改造，使其在细胞内产生一种标记，从而产生每一个连接蛋白。通过一个简单的反应，我们可以在组织切片中看到产生连接蛋白的细胞。由于脑干和脊髓含有不同功能的神经元，我们将使用额外的解剖学和生理学方法来确定哪些细胞类型表达特定的连接蛋白。我们还将用不同类型的标记杂交小鼠，看看一个细胞是否可以产生一种以上的连接蛋白。这一点很重要，因为单个细胞中不同连接蛋白的存在可能会影响特定间隙连接的工作方式。因此，这些研究将提供有关神经元连接蛋白的分布、细胞类型和共定位的新数据。由于我们的初步研究表明，连接蛋白的存在，在神经元组以前不知道表达间隙连接，全面的分析可能会揭示新的人口为未来的研究。识别出这些具有同步活动能力的神经元群，将为理解这些大脑区域的功能提供新的领域。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Localization of neurones expressing the gap junction protein Connexin45 within the adult spinal dorsal horn: a study using Cx45-eGFP reporter mice.

DOI：
10.1007/s00429-012-0426-1
发表时间：
2013-05
期刊：
BRAIN STRUCTURE & FUNCTION
影响因子：
3.1
作者：
Chapman, R. J.;Lall, V. K.;Maxeiner, S.;Willecke, K.;Deuchars, J.;King, A. E.
通讯作者：
King, A. E.

The anti-malarial drug Mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat.

DOI：
10.1186/1423-0127-19-103
发表时间：
2012-12-15
期刊：
Journal of biomedical science
影响因子：
11
作者：
Lall VK;Dutschmann M;Deuchars J;Deuchars SA
通讯作者：
Deuchars SA

Physiologic regulation of heart rate and blood pressure involves connexin 36-containing gap junctions.

心率和血压的生理调节涉及连接36的间隙连接。

DOI：
10.1096/fj.201600919rr
发表时间：
2017-09
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
0
作者：
Lall VK;Bruce G;Voytenko L;Drinkhill M;Wellershaus K;Willecke K;Deuchars J;Deuchars SA
通讯作者：
Deuchars SA

A new conditional mouse mutant reveals specific expression and functions of connexin36 in neurons and pancreatic beta-cells.

一种新的条件小鼠突变体揭示了神经元和胰腺β细胞中连接蛋白36的特定表达和功能。