The level of neurotrophins in the brain of mice with urokinase gene knockout in experimental melanoma and comorbid pathology

Abstract

The objective was to evaluate the levels of neurotrophins in the brain of mice with urokinase (uPA) gene knockout, carriers of B16/F10 melanoma developing in presence of comorbid pathology – chronic neurogenic pain (CNP).Methods and materials. The study included female mice of two strains: С57ВL/6 (n=40) and C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu (n=28). In the main groups, CNP was created by the bilateral sciatic nerve ligation, with В16/F10 melanoma transplanted under the skin of the back 2 weeks after. The comparison groups included sham operated animals with melanoma transplantation, the control groups – sham operated animals and animals with CNP. Mice were decapitated on day 21 of the tumor growth, and the brain levels of brain neurotrophic factor (BDNF); nerve growth factor (NGF), neurotrophins 3 (NT3) and 4 (NT4) were studied by ELISA.Results. The brain of mice with uPA gene knockout demonstrated higher levels of NT3 (by 1.3 times (p=0.0146)), NT4 (by 2.6 times) and NGF-β (by 1.9 times (p=0.0021)) and lower BDNF (by 1.7 times (p=0.0203)), compared to mice without knockout. Cerebral reduction of NGF-β was a nonspecific brain response to CNP and neoplastic growth in female mice, enhanced in the combination of the pathological factors. Greater stimulation of subcutaneous melanoma growth in female mice with uPA knockout under the influence of CNP combined with a 2-fold decrease in levels of NT3 and BDNF in the brain, along with 2.2 times higher cerebral levels of NGF-β, compared to female mice without knockout.Conclusions. In female mice with uPA gene knockout compared to mice without knockout, we revealed background differences and other dynamics of neurotrophin levels in the brain at melanoma growth both alone and in combination with comorbid pathology – CNP.