Midbrain dopamine systems and control of bladder function

尿激性尿失禁(UUI)：？一种难以推迟的突如其来的强烈排尿欲望？是一个广泛存在的临床问题，尤其是老年人，据报道其发病率为12-17%。最新的现有数据(1997年)估计，英国卫生预算的成本为5.36亿英镑，然而，尽管UUI产生了巨大的社会经济影响，但仍然没有得到有效的管理。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以接受的地方，如卫生间。有了UUI，推迟膀胱排空的能力就会丧失。目前的药物治疗针对的是膀胱肌，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，以及神经细胞用来相互交流的化学神经递质还不完全清楚。在开发任何治疗UUI的新方法之前，更清楚地了解膀胱控制电路的正常功能是必不可少的。目前的方案使用了老鼠模型，旨在更全面地了解正常动物的这些大脑回路。其目的是将一种名为光遗传学的强大的新方法结合在一起。(光对神经元的激活/灭活)，这是一种基于病毒的神经元连接映射工具，使用经典的生理测量来研究控制膀胱功能的大脑电路。这项研究的新数据将为开发具有正常化作用的新药提供必要的信息。失控的UUI患者的膀胱控制回路的活动。

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.