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Войти в исследования Gaceta medica de Mexico · 2022
Diabetes mellitus causes changes in the activity and expression of brain tryptophan-5-hydroxylases and in the number of serotonergic neurons, which do not return to normal with insulin treatment.
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Manjarrez-Gutiérrez Gabriel, Mondragón-Herrera José Antonio, Hernández-Rodríguez Jorge
Аннотация
INTRODUCTION: Diabetes mellitus (DM) inhibits brain serotonin biosynthesis through changes in tryptophan-5-hydroxylase (TPH) activity and expression.
OBJECTIVES: To determine whether DM-induced changes in brain TPH1 or TPH2 expression and in the number of serotonergic neurons return to normal in diabetic rats treated with insulin.
METHODS: Rats with streptozotocin-induced diabetes were divided in two groups: one treated with insulin and the other without treatment. On day 14, brain stems were obtained in order to quantify L-tryptophan and 5-hydroxytryptamine levels, as well as to determine TPH activity. The expression of TPH1 and TPH2 by West-ern blot, and the number of serotonergic neurons by immunohistochemistry.
RESULTS: In diabetic rats, a decrease in the levels of L-tryptophan, 5-hydroxytryptamine, and TPH activity was confirmed, as well as lower TPH1 and TPH2 expression and lower numbers of serotonergic neurons. When diabetic rats were treated with insulin, L-tryptophan returned to normal, but not 5-hy-droxytryptamine, TPH expression, or the number of serotonergic neurons.
CONCLUSIONS: DM chronically inhibits the synthesis of brain 5-hydroxytryptamine through changes in TPH1 and TPH2 expression and a decrease in the number of serotonergic neurons, which persist despite insulin treatment.
OBJECTIVES: To determine whether DM-induced changes in brain TPH1 or TPH2 expression and in the number of serotonergic neurons return to normal in diabetic rats treated with insulin.
METHODS: Rats with streptozotocin-induced diabetes were divided in two groups: one treated with insulin and the other without treatment. On day 14, brain stems were obtained in order to quantify L-tryptophan and 5-hydroxytryptamine levels, as well as to determine TPH activity. The expression of TPH1 and TPH2 by West-ern blot, and the number of serotonergic neurons by immunohistochemistry.
RESULTS: In diabetic rats, a decrease in the levels of L-tryptophan, 5-hydroxytryptamine, and TPH activity was confirmed, as well as lower TPH1 and TPH2 expression and lower numbers of serotonergic neurons. When diabetic rats were treated with insulin, L-tryptophan returned to normal, but not 5-hy-droxytryptamine, TPH expression, or the number of serotonergic neurons.
CONCLUSIONS: DM chronically inhibits the synthesis of brain 5-hydroxytryptamine through changes in TPH1 and TPH2 expression and a decrease in the number of serotonergic neurons, which persist despite insulin treatment.