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Gaceta médica de México

versão On-line ISSN 2696-1288versão impressa ISSN 0016-3813

Resumo

MANJARREZ-GUTIERREZ, Gabriel; MONDRAGON-HERRERA, José Antonio  e  HERNANDEZ-RODRIGUEZ, Jorge. Diabetes mellitus causes changes in brain tryptophan-5-hydroxylases activity and expression and in the number of serotonergic neurons, which do not return to normal with insulin treatment. Gac. Méd. Méx [online]. 2022, vol.158, n.4, pp.190-197.  Epub 30-Set-2022. ISSN 2696-1288.  https://doi.org/10.24875/gmm.22000100.

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 and 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 expressión of TPH1 and THP2 by Western 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-hydroxytryptamine, 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.

Palavras-chave : Diabetes mellitus; Insulin; Serotonin; Tryptophan-5-hydroxylases; Serotonergic neurons.

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