Midbrain dopamine systems and control of bladder function

尿急指数（UUI）：？突然强烈的排尿欲望难以抑制是一个普遍的临床问题，特别是老年人，据报道其发病率为12-17%。最新的可用数据（从1997年开始）估计，联合王国的卫生预算费用为5.36亿英镑，然而，尽管UUI具有巨大的社会经济影响，但它仍然没有得到有效管理。正常情况下，成年人能够抑制他们的膀胱排空，即使它是满的，直到他们发现自己在一个安全和社会可接受的地方，如浴室。使用UUI，延迟膀胱排空的能力丧失。目前的药物治疗针对膀胱肌肉，目的是降低其兴奋性。然而，主要原因可能不在于膀胱本身，而在于调节膀胱充盈和排空的中枢控制通路。目前，这些通路在大脑中的确切位置以及神经细胞相互交流所使用的化学神经递质还没有完全了解。在开发任何新的UUI治疗方法之前，更清楚地了解膀胱控制电路的正常功能是必不可少的。目前的提议使用小鼠模型，旨在更全面地了解正常动物的这些大脑回路。其目的是将联合收割机与一种名为？光遗传学？（通过光激活/灭活神经元），一种基于病毒的神经元连接映射工具，具有经典的生理测量以研究控制膀胱功能的脑回路。这项研究的新数据将提供开发新药所需的基本信息，这些新药的作用是？正常化？膀胱控制回路的活动在那些患有UUI的个体中已经失去控制。

Urinary Urge Incontinence (UUI): ?a sudden compelling desire to pass urine which is difficult to defer? is a widespread clinical problem that especially the elderly in whom an incidence of 12-17% is reported. The latest available figures (from 1997) estimated a cost to the UK health budget of #536 million, yet despite its enormous socioeconomic impact UUI is still not managed effectively. Normally, adult humans are able to inhibit their bladder from emptying, even when it is full, until they find themselves in a safe and socially acceptable place such as a bathroom. With UUI the ability to defer bladder emptying is lost. Current drug treatments target the bladder muscle, with the aim of reducing its excitability. However, the primary cause may lie not in the bladder itself, but in the central control pathways that regulate bladder filling and emptying. At present the precise location of these pathways in the brain and the chemical neurotransmitters employed by the nerve cells to communicate with each other are not fully understood. A clearer understanding of the normal function of the bladder control circuitry is essential before any new treatment for UUI can be developed. The current proposal, which uses a mouse model, has been designed to provide a fuller understanding of these brain circuits in normal animals. The aim is to combine a powerful new method called ?optogenetic? (activation/inactivation of neurons by light), a virus-based neuron connectivity mapping tool with classical physiological measurements to study brain circuitry that controls bladder function. The new data from the study will provide the essential information needed for developing new drugs that act to ?normalise? the activity of the bladder control circuits in those individuals with UUI in whom the control has been lost.