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The effect of prolonged intranasal administration of serotonin on the activity of hypothalamic signaling systems in male rats with neonatal diabetes

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Abstract

The functioning of the serotonergic system of the brain is impaired in type II diabetes (T2D), and this leads to metabolic and hormonal dysfunction. The elevation of serotonin level in the CNS is one of the approaches for correcting of the serotonergic system of the brain. The aim of the present work was to investigate the effect of intranasal serotonin (InS) administration for 5 weeks at a daily dose of 20 μg on the metabolic parameters and functional activity of adenylate cyclase signaling system (ACSS) sensitive to peptide hormones and biogenic amines in the hypothalamus of male rats with neonatal T2D. Neonatal model of T2D was induced by injecting streptozotocin (70 mg/kg) into 5-day-old rat pups. Four-month-old animals with apparent T2D manifestations were divided into two groups: an untreated group (D0, n = 6) and a group that received InS treatment (DIS, n = 6). InS administration to diabetic rats restored ACSS regulation by the agonists of type 2 dopamine receptors (DA2R) and type 4 melanocortin receptors (MC4R) and enhanced the inhibitory effect of serotonin on adenylate cyclase activity. Elevated expression of genes encoding DA2R, MC4R, and serotonin receptor of the 1B subtype (5-HT1BR) was among the main causes of this change. The relative activity of signaling cascades involving various types of serotonin (Gs-coupled 5-HT4,6,7R/Gi-coupled 5-HT1R), dopamine (DA1R/ DA2R), and melanocortin (MC3R/MC4R) receptors involved in ACSS regulation was also altered in the animals of the DIS group. InS administration restored hormonal regulation in the hypothalamus, improved glucose tolerance, and increased the sensitivity of tissues to insulin. The data obtained show that the elevation of serotonin level in the CNS is a promising approach for the recovery of hypothalamic signaling pathways in T2D and correction of the metabolic disturbances dependent on these pathways.

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Abbreviations

AC:

adenylate cyclase

ACSS:

adenylate cyclase signaling system

GTT:

glucose tolerance test

DAR (including DA1R and DA2R):

dopamine receptors (including type 1 and type 2 receptors)

IGTT:

insulin glucose tolerance test

MC3R and MC4R:

type 3 and type 4 melanocortin receptors

T1D and T2D:

type 1 and type 2 diabetes mellitus

SSRI:

selective serotonin reuptake inhibitor

5-HTR (including 5-HT1R and 5-HT6R):

serotonin receptors (including type 1 and type 6 serotonin receptors)

Gs- and Gi-proteins:

stimulatory and inhibitory G-proteins

PACAP-38:

pituitary adenylyl cyclase-activating polypeptide-38

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, 194223, Russia

    I. B. Sukhov, K. V. Derkach, O. V. Chistyakova, V. M. Bondareva & A. O. Shpakov

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  1. I. B. Sukhov
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  2. K. V. Derkach
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  3. O. V. Chistyakova
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  4. V. M. Bondareva
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  5. A. O. Shpakov
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Correspondence to A. O. Shpakov.

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Original Russian Text © I.B. Sukhov, K.V. Derkach, O.V. Chistyakova, V.M. Bondareva, A.O. Shpakov, 2016, published in Tsitologiya, 2016, Vol. 58, No. 3, pp. 219–228.

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Sukhov, I.B., Derkach, K.V., Chistyakova, O.V. et al. The effect of prolonged intranasal administration of serotonin on the activity of hypothalamic signaling systems in male rats with neonatal diabetes. Cell Tiss. Biol. 10, 314–323 (2016). https://doi.org/10.1134/S1990519X1604012X

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  • DOI: https://doi.org/10.1134/S1990519X1604012X

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