Levels of neurotrophins in the brain of female rats in an experimental model of malignant tumor growth under conditions of hypothyroidism

Abstract

Objective. Studying the levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF-β), and neurotrophin 3 (NT3) in the cerebral cortex and subcortical substance of female rats in an experimental model of extracerebral growth of malignant tumor under conditions of induced hypothyroidism.Materials and methods. An experiment was performed on 47 white non-linear female rats: 10 rats each in the intact group, control group 1 (induced hypothyroidism), control group 2 (subcutaneous growth of Guerin’s carcinoma), main group (combination of pathologies); 7 rats in the group with subcutaneous tumor growth to assess life expectancy. Hypothyroidism was induced by per os administration of thiamazole (mercazolil, Akrikhin, Russia), daily dose of 2.5 mg/100 g of body weight, course of 30 days; total thyroxine and thyroid stimulating hormone were determined in blood serum by RIA (Immunotech, Czech Republic). When persistent hypothyroidism was achieved, Guerin’s carcinoma was transplanted under the skin as standard. Aſter decapitation on the 18th day aſter transplantation, the content of BDNF, NGF-β, NT3 (R&D System, RayBiotech, USA) was determined in 10 % homogenates of the cortex and subcortical substance subcortex of the brain (R&D System, RayBiotech, USA).Results. In the cortex in control groups 1 and 2, the level of BDNF was 2.6- and 1.6-fold lower, respectively, and NGF-β was 2.2-fold higher on average than in the intact group. NT3 levels in the control group 1 were 3.0- and 1.6-fold lower in the cortex and subcortical substance, respectively. In the control group 2, the levels of NT3 and NGF-β were higher in the subcortical matter than in the intact group by 2.4-fold and 3.1-fold, respectively. In the cortex and subcortical substance in the main group, only NGF-β levels were higher on average by 1.7 times, with values being intermediate between the corresponding values in control groups 1 and 2.Conclusion. Changes in the levels of all neurotrophins in hypothyroidism were most pronounced in the cortex, while in independent tumor growth, NGF-β in the cortex and subcortical substance and NT3 only in subcortical substance changed the most. When the pathologies were combined, only NGF-β was altered in the cortex and subcortical substance. Apparently, there is an interaction of the tumor and the CNS with changes in the balance of regulatory signals in the subcortical areas of the brain, that reflecting the connection with the biological characteristics of an active or inhibited (in presence of hypothyroidism) tumor growth.

Keywords

• tumor process
• thyroid dysfunction
• comorbidity
• hypothyroidism
• guerin's carcinoma
• brain
• neurotrophins
• brain-derived neurotrophic factor
• nerve growth factor
• neurotrophin 3
• female rats
• experimental model