Age-related alteration of neurturin receptor GFRa2 and nNOS in pelvic ganglia

Neurturin is a neurotrophic factor that is widely expressed in cavernous tissue and retrogradely transported to penis-projecting neurons via its receptor, glial cell line derived neurotrophic factor family receptor alpha-2 (GFRa2). To investigate the influence of aging on neural function on the penis, we examined the expression of GFRa2 mRNA in the major pelvic ganglion and its relationship to neuronal nitric oxide synthase (nNOS)- and tyrosine hydroxylase (TH)-positive neurons. GFRa2 and nNOS mRNA expression levels in RT-PCR showed age-related decreases in 1-, 3-, 6-, 12-, 18- and 24-month-old rats. In situ hybridization also revealed that the number of GFRa2-positive neurons in pelvic ganglia decreased with aging. A double-labeling study revealed the co-expression of GFRa2 and nNOS, which simultaneously decreased in old adult (24 months) and young castrated rats compared with young adult rats (3 months). These results suggest that aging and castration influence the numbers of nNOS- and GFRa2-positive neurons. Higher age might affect not only cavernous tissue but also the neural plasticity of the cavernous nerve related to erectile function.