Vasopressin and the retina

加压素和视网膜

• 批准号: MR/M022838/1
• 负责人: Mike Ludwig
• 金额: $ 78.95万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM022838%2F1
• 关键词: Vasopressin; retina

All living beings are synchronized to the rhythmic light-dark changes that occur daily. These daily (circadian) rhythms are generated by internal biological 'clocks', and these clocks are co-ordinated by specialized neurons in one special region of the brain - the suprachiasmatic nucleus (SCN). The activity of the SCN is synchronized daily by environmental signals - mainly by information on light received by the retina, which is communicated by nerve fibers to the SCN.Exactly how the retinal input entrains the rhythm of the SCN is unclear. Several mechanisms, including gene activation and local neuropeptide release, have been linked to the regulation of this 'clock'. Signaling of the neuropeptide vasopressin in the SCN plays a particularly important role - vasopressin is critical for re-setting of the clock after a change in the light-dark cycle, for example during transcontinental travelling or shift work. The SCN contains a large population of vasopressin neurons, but we recently found that the retina also contains many vasopressin-expressing cells, and that, strikingly, these communicate exclusively with the SCN - they are involved only with regulating circadian rhythms, and not with normal vision. Thus, these newly discovered vasopressin cells in the retina are a major, light-activated pathway that has a key role in regulating important circadian rhythms. The proposed research will define exactly how these cells influence the SCN, and will establish how modulation of the retina-SCN pathway contributes to changes in circadian rhythm regulation. The experimental studies will all be on laboratory rats - and will include studying the effects of selectively destroying or activating these cells using very sophisticated genetic approaches. These approaches will involve inserting a gene into these retinal vasopressin cells to enable their activity to be controlled precisely in experiments that will be carried out in deeply anesthetized rats. The SCN is part of the hypothalamus of the brain; in evolutionary terms, this is an ancient structure that is present in all vertebrates. The SCN is organised in a very similar way in all mammalian species that have been studied, so findings from studies in the rat are likely to be "translatable" into understanding of how rhythms are regulated in people. Identifying a specific population of cells in the retina that has a key and selective role in regulating body rhythms will open up new therapeutic possibilities for helping to restore altered circadian rhythms during jet lag or rotating shift work. Epidemiology shows that rotational shift work is accompanied by major health risks, including increased propensity for cancer, depression, sleep disturbances, gastrointestinal, metabolic and cardiovascular disorders, decreased immune responses and even life span.

所有生物都与每天发生的有节奏的明暗变化同步。这些日常（昼夜节律）节律是由内部生物“时钟”产生的，这些时钟由大脑一个特殊区域——视交叉上核（SCN）中的专门神经元协调。 SCN 的活动每天通过环境信号同步 - 主要是通过视网膜接收到的光信息，这些信息通过神经纤维传递到 SCN。视网膜输入究竟如何影响 SCN 的节律尚不清楚。多种机制，包括基因激活和局部神经肽释放，都与这个“时钟”的调节有关。 SCN 中神经肽加压素的信号传导发挥着特别重要的作用 - 加压素对于明暗周期变化后重置时钟至关重要，例如在跨大陆旅行或轮班工作期间。 SCN 含有大量的加压素神经元，但我们最近发现视网膜也含有许多表达加压素的细胞，令人惊讶的是，这些细胞只与 SCN 进行通信——它们只参与调节昼夜节律，与正常视力无关。因此，视网膜中这些新发现的加压素细胞是一种主要的光激活途径，在调节重要的昼夜节律中发挥着关键作用。拟议的研究将准确定义这些细胞如何影响 SCN，并将确定视网膜-SCN 通路的调节如何促进昼夜节律调节的变化。实验研究将全部针对实验室老鼠，包括研究使用非常复杂的遗传方法选择性破坏或激活这些细胞的影响。这些方法将涉及将基因插入这些视网膜加压素细胞中，以便在深度麻醉的大鼠中进行的实验中能够精确控制它们的活性。 SCN 是大脑下丘脑的一部分；从进化的角度来看，这是一种存在于所有脊椎动物中的古老结构。在所有已研究的哺乳动物物种中，视交叉上核的组织方式非常相似，因此对大鼠的研究结果很可能“转化”为对人类节律如何调节的理解。识别视网膜中在调节身体节律方面具有关键和选择性作用的特定细胞群，将为帮助恢复时差或轮班工作期间改变的昼夜节律开辟新的治疗可能性。流行病学表明，轮班工作伴随着重大健康风险，包括癌症、抑郁、睡眠障碍、胃肠道、代谢和心血管疾病的倾向增加，免疫反应下降，甚至寿命缩短。

项目成果

Dendritic Release of Neurotransmitters.

神经递质的树突释放。

• DOI: 10.1002/cphy.c160007
• 发表时间: 2016-12-06
• 期刊: Comprehensive Physiology
• 影响因子: 5.8
• 作者: Ludwig M;Apps D;Menzies J;Patel JC;Rice ME
• 通讯作者: Rice ME

NOTE: Effects of lateral olfactory tract stimulation on Fos immunoreactivity in vasopressin neurones of the rat piriform cortex

注: 侧嗅道刺激对大鼠梨状皮层加压素神经元 Fos 免疫反应性的影响

• DOI: 10.1111/jne.12637
• 发表时间: 2018
• 期刊: Journal of Neuroendocrinology
• 影响因子: 3.2
• 作者: Tsuji C

Coding of odors in the anterior olfactory nucleus.

前嗅核中的气味编码。

• DOI: 10.14814/phy2.14284
• 发表时间: 2019
• 期刊: Physiological reports
• 影响因子: 2.5
• 作者: Tsuji T

Effects of optogenetic stimulation of vasopressinergic retinal afferents on suprachiasmatic neurones.

血管加压能视网膜传入的光遗传学刺激对视交叉上神经元的影响。

• DOI: 10.1111/jne.12806
• 发表时间: 2019
• 期刊: Journal of neuroendocrinology
• 影响因子: 3.2
• 作者: Hume C

Effect of Melanotan-II on Brain Fos Immunoreactivity and Oxytocin Neuronal Activity and Secretion in Rats.

Melanotan-II 对大鼠脑 Fos 免疫反应性和催产素神经元活性和分泌的影响。

• DOI: 10.1111/jne.12454
• 发表时间: 2017
• 期刊: Journal of neuroendocrinology
• 影响因子: 3.2
• 作者: Paiva L