Expression of apoptosis-regulating genes in the rat prostate following botulinum toxin type a injection

Adult Wistar rats were injected in the ventral lobes of the prostate with 10 U of OnabotA or saline. A set of OnabotA-injected animals was further treated with 0.5 mg/kg of phenylephrine (PHE) subcutaneously daily. All animals were sacrificed after 1 week and had their prostates harvested. Immunohistochemical staining was performed for Bax, Bcl-xL and caspase-3 proteins and visualized by the avidin-biotin method. The optical density of the glandular cells was also determined, with measurement of differences between average optical densities for each group.Saline-treated animals showed intense epithelial staining for Bcl-xL and a faint labelling for both Bax and Caspase-3. OnabotA-treated rats showed a reduced epithelial staining of Bcl-xL and a consistently increased Bax and Caspase-3 staining when compared with saline-treated animals. PHE-treated animals showed a stronger Bcl-xL staining and reduced staining of both Bax and Caspase-3 when compared to the OnabotA group. Mean signal intensity measurements for each immunoreaction confirmed a significant decrease of the signal intensity for Bcl-xL and a significant increase of the signal intensity for Bax and Caspase 3 in OnabotA-injected animals when compared with the control group. In OnabotA+PHE treated animals mean signal intensity for Bcl-xL, Bax and Caspase 3 immunoreactions was identical to that of the control animals.These results support the hypothesis that OnabotA activates apoptotic pathways in the rat prostate through a mechanism that involves sympathetic outflow impairment.Botulinum toxin type A (BoNT/A) is one of seven serotypes of a neurotoxin produced by Clostridium botulinum. The toxin binds synaptic vesicle type 2 (SV2) expressed on the neuronal surface at points where synaptic vesicles fuse with the cytoplasmatic membrane. When synaptic vesicles are recycled, the neurotoxin, attached to SV2, is internalized and later cleaved into a light and heavy chain. The former is responsible for the inactivation