Abstract
Aim . Studying the influence of the features of aminergic brain status on the development of B16/F10 melanoma in mice with urokinase gene knockout and chronic neurogenic pain (CNP). Material and methods . The study included female ( n = 68) С57ВL/6 mice with the normal urokinase gene (+ uPA ) and C57BL/6-PlautmI.IBug-This Plau6FDhu/GFDhu mice with urokinase gene knockout (– uPA ). The model of CNP was created in the animals, and in 14 days B16/F10 melanoma was transplanted. The mice were euthanized 21 days after the transplantation. Levels of adrenaline (A), noradrenaline (NA), dopamine (DA), histamine (H), serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA) were determined in the brain using standard ELISA test systems (Cusabio, China). Results . CNP in (+ uPA ) females resulted in the reduction of almost all studied biogenic amines (BA). On the opposite, (– uPA ) females showed an increase in NA, DA, 5HT and a decrease of H. 5HIAA increased in both CNP and gene knockout. 5HT in (+ uPA ) females with CNP decreased, while its physiological level in gene knockout mice was maintained. After 3 weeks of tumor growth in animals with CNP, (+ uPA ) mice demonstrated increased levels of studied BA (except for 5HIAA) compared to mice with CNP alone. Only H increase was observed in (– uPA ) mice from the similar group. Conclusion. CNP in mice inhibited A-, NA-, H- and 5HT-ergic systems of the brain; the opposite effects were registered in urokinase gene knockout, except for the H-ergic system. Combination of CNP and melanoma in (+ uPA ) female mice activated all studied BA systems, and in (– uPA ) females – H-ergic system only. Different stressful effects, CNP, and genetic disorders (urokinase gene knockout) contributed to changes in the brain BA system functions, leading to the activation of pro- or antitumor mechanisms.
Highlights
The model of chronic neurogenic pain (CNP) was created in the animals, and in 14 days B16/F10 melanoma was transplanted
CNP in (+uPA) females resulted in the reduction of almost all studied biogenic amines (BA)
On the opposite, (–uPA) females showed an increase in NA, DA, 5HT and a decrease of H. 5-hydroxyindoleacetic acid (5HIAA) increased in both CNP and gene knockout. 5HT in (+uPA) females with CNP decreased, while its physiological level in gene knockout mice was maintained
Summary
Изучить влияние особенностей аминергического статуса головного мозга у мышей при нокауте гена урокиназы и хронической нейрогенной боли (ХНБ) на развитие меланомы В16/F10. Обнаружено увеличение уровня 5ОИУК при ХНБ и нокауте. У самок (+uPA) с ХНБ снижался уровень 5НТ, но сохранялось его физиологическое содержание у мышей с нокаутом. Через 3 нед роста опухоли на фоне ХНБ у мышей (+uPA) обнаружено увеличение уровня всех изученных БА, кроме 5ОИУК, по сравнению с уровнем у мышей только с ХНБ. ХНБ приводила к угнетению А-, НА-, Г-, 5НТ-ергических систем мозга мышей, а при нокауте гена урокиназы наблюдались противоположные эффекты, за исключением Г-ергической системы. Сочетание ХНБ и меланомы у самок мышей (+uPA) приводило к активации всех изученных систем БА, а у самок (–uPA) – только Г-ергической системы. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи.
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