Study of neuroplastic centrally induced bladder hyper activity and gene therapy

我们用一些疾病大鼠模型研究了中枢性膀胱亢进。膀胱出口梗阻，如良性前列腺肥大正成为常见病，从而引起膀胱亢进。这种过度活跃可能是由于中枢神经控制排尿功能紊乱所致。在本研究中，我们可以证明，在棘上水平，速激肽和α1肾上腺素受体也可能参与排尿控制，特别是在膀胱出口梗阻大鼠中。提示椎管上NK受体和肾上腺素能受体可能是药物治疗膀胱出口梗阻继发性膀胱亢进的靶点。脑桥蓝斑区是诱发帕金森病症状的重要区域之一。我们发现，1-多巴刺激蓝斑可诱导膀胱过度活动，并被速激肽受体拮抗剂抑制，多巴胺1受体拮抗剂的缺乏可能在帕金森病中发挥膀胱过度活动的作用。随着年龄的增长，排尿的神经控制发生变化，其机制不能仅用肾上腺素能和副交感神经控制来解释。5-羟色胺受体广泛分布于中枢神经系统，包括控制排尿反射通路的几个区域。我们发现，作用于5-HT1A、5-HT2和5-HT4受体的5-HT受体拮抗剂可能成为治疗膀胱多动症药物的靶点。

We studied the centrally induced bladder hyperactivity by using some disease rat models.Bladder outlet obstruction, such as benign prostatic hypertrophy is becoming common disease, which causes bladder hyperactivity. This hyperactivity may results from the disorders of the central nervous control of the micturition. In this study, we could demonstrate that, at the supraspinal level, tachykinin and α1 adrenoceptors may also be involved in micturition control, especially in the rats with bladder outlet obstruction. The results imply that supraspinal NK receptors and adrenergic receptors are a possible target for drugs aimed for elimination of bladder hyperactivity secondary to bladder outlet obstruction.Locus coerules in pons is one of the important areas to induce the symptoms of Parkinson's disease. We showed that stimulation of locus coeruleus by 1-dopa induces bladder overactivity and suppressed by tachykinin receptor antagonists, and also the lack of dopamine 1 receptor antagonist may play a role of overactive bladder in Parkinson's disease.By aging, the nervous control of micturition changes and the mechanism cannot be explained by only adrenergic and parasympathetic nervous control. 5-HT receptors are widely distributed in the central nervous system, including several areas involved in the-control of micturition reflex pathways. We showed that 5-HT receptor antagonists,-acting at 5-HT1A, 5-HT2 and 5-HT4 receptors, could be targets for drugs meant for treatment of bladder hyperactivity.