Rickey Leslie Minor, Sarkey Sara, DonCarlos Lydia L
Division of Urology, University of Maryland Medical Center, Baltimore, Maryland 21201, USA.
Neurourol Urodyn. 2008;27(5):440-5. doi: 10.1002/nau.20522.
Urinary incontinence affects a significant number of post-menopausal women. There is conflicting evidence whether voiding symptoms in these women are related to hypoestrogenism or aging itself. This neuroanatomical study was designed to determine whether a specific central nervous system (CNS) pathway that projects to the pontine micturition center (PMC, also known as "Barrington's nucleus") is estrogen sensitive in a rat model.
A fluorescent retrograde tracer was injected into the dorsal pontine tegmentum of adult female Sprague-Dawley rats to identify neurons in the medial preoptic area (MPA) that project to the PMC. Immunohistochemistry was performed using antibodies directed against estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) to identify estrogen-sensitive neurons. The brain sections were examined using fluorescence microscopy to identify cells that project to the PMC (contain fluorescent tracer) and also express ER (are immunoreactive for ER).
There are neurons in the MPA that are double labeled (contain fluorescent tracer and express ERalpha, but not ERbeta), showing that a subset of neurons projecting from the MPA to the PMC is estrogen sensitive.
A subset of estrogen-sensitive neurons projects from the MPA to the PMC in rats, raising the possibility that indirect estrogenic regulation of forebrain neuronal function may modulate the micturition reflex. Future development of drugs that alter the function of this estrogen-sensitive CNS pathway may provide therapeutic strategies to treat post-menopausal incontinence.
尿失禁影响大量绝经后女性。关于这些女性的排尿症状是与雌激素缺乏还是衰老本身相关,存在相互矛盾的证据。本神经解剖学研究旨在确定在大鼠模型中,投射至脑桥排尿中枢(PMC,也称为“巴林顿核”)的特定中枢神经系统(CNS)通路是否对雌激素敏感。
将荧光逆行示踪剂注入成年雌性斯普拉格 - 道利大鼠的脑桥背侧被盖区,以识别投射至PMC的视前内侧区(MPA)中的神经元。使用针对雌激素受体α(ERα)和雌激素受体β(ERβ)的抗体进行免疫组织化学,以识别雌激素敏感神经元。使用荧光显微镜检查脑切片,以识别投射至PMC(含有荧光示踪剂)且还表达ER(对ER免疫反应)的细胞。
MPA中存在双标记神经元(含有荧光示踪剂并表达ERα,但不表达ERβ),表明从MPA投射至PMC的神经元亚群对雌激素敏感。
在大鼠中,一个雌激素敏感神经元亚群从MPA投射至PMC,这增加了前脑神经元功能的间接雌激素调节可能调节排尿反射的可能性。改变这种雌激素敏感CNS通路功能的药物的未来开发可能为治疗绝经后尿失禁提供治疗策略。