Login to Access Video or Poster Abstract: MP45-09
Sources of Funding: None

Introduction

A third of men diagnosed with prostate cancer will undergo radiation therapy (RT) which frequently results in erectile dysfunction (ED). Prostatic radiation is presumed to cause damage to the vasculature and the nerves supplying the penis. There are no effective treatment strategies to prevent or recover radiation-induced ED which significantly impacts the quality of life of prostate cancer survivors. This study examined the impact of low and high radiation on neurite growth, branching and survival of sympathetic and nitrergic neurons cultured from the major pelvic ganglia (MPG).

Methods

MPGs collected from male Sprague-Dawley rats (n=6) were dissociated and neurons plated on laminin coated glass cover slips. After 24 hours, neurons were irradiated at 2Gy or 8Gy, grown for an additional 48 hours and then compared to time-matched control neurons. Neurons were fixed and stained with immunofluorescence for neuron-specific class III beta-tubulin to measure axon length and branching, neuronal nitric oxide synthase (nNOS, nitrergic), tyrosine hydroxylase (TH; sympathetic) or TUNEL assay for apoptosis. Images were taken of all neurons on each cover slip at a magnification of 100x.

Results

Neurite length was unchanged with radiation, however, neurite branching significantly decreased with both doses of radiation (CON: 3.0±0.11, 2Gy: 2.6±0.16, 8Gy: 2.5±0.16; p<0.005). There was a 3 to 4-fold increase in the percentage of apoptotic TUNEL positive neurons in both groups following radiation (p<0.0001). There was no change in the relative number of sympathetic TH positive neurons with radiation. In contrast, a marked decrease in nNOS positive neurons increased with the dose of radiation (CON: 45±4.4%, 2Gy: 20±3.1%, 8Gy: 5±0.7%; p<0.0001).

Conclusions

These data demonstrate that RT stimulates an increase in neuronal cell death and a substantial decrease in the number of erectile promoting nitrergic neurons. Although there is no change in neurite length, neurite branching which is essential for the establishment of appropriate neuronal connections and regeneration was impaired. Future studies will examine the impact of prostatic RT in an animal model to determine if these neuronal impairments contribute to ED in order to elucidate the pathological mechanisms to lead to new therapeutic radioprotection strategies for prostate cancer survivors.

Funding

None