Estrogen-sensitive projections from the medial preoptic area to the dorsal pontine tegmentum, including Barrington's nucleus, in the rat

Aim: 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. Methods: 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 (ER alpha) and estrogen receptor-beta (ERP) 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). Results: There are neurons in the MPA that are double labeled (contain fluorescent tracer and express ERa, but not ER beta), showing that a subset of neurons projecting from the MPA to the PMC is estrogen sensitive. Conclusions: 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.