TY - JOUR

T1 - TpH2 expression after neonatal dexamethasone treatment and acute or chronic stress in adulthood

AU - Kalinina, T.

AU - Sukhareva, E.

AU - Lanshakov, D.

AU - Bulygina, V.

AU - Dygalo, N.

PY - 2019

Y1 - 2019

N2 - Background: Dysregulation of serotonergic (5-HT) brain system is implicated in a number of neuropsychiatric disorders including depression, anxiety, obsessive-compulsive disorder as well as autism spectrum disorder. Vulnerability to anxiety and affective disorders in adulthood is dramatically increased after early-life stressful experience. Adverse early-life conditions are accompanied by an increase of glucocorticoid hormones. As we have shown previously, administration of dexamethasone (DEX), a specific synthetic glucocorticoid receptors agonist, reduced the neuronal tryptophan hydroxylase (TpH2) expression, the rate-limiting enzyme for 5-HT synthesis, in the midbrain of the neonatal rats [1]. Here, we tested the hypothesis that overexposure to DEX during neonatal development has programming effects on the brain, resulting in altered behaviors and TpH2 expression in adulthood. Methods: Dexamethasone (DEX) was subcutaneously administered in the therapeutic dose range (0.2 mg/kg) to male rat pups on 3rd day of life (PD3). Control groups were consisting of intact and saline-treated pups. A within-litter design was used to minimize variation in maternal care. After weaning (PD25), animals were kept in litters up to behavioral tests. A protocol of chronic unpredictable mild stress (CUMS) for 15 consecutive days (from PD45 to PD60) during which the presentation of stressors such as bright light, food deprivation, short restriction, hot air, among others, were made. Force swim test (FST) on PD60 was used as acute stress. All animals were also tested for anxiety-like behavior in elevated plus-maze (EPM) on PD52. Brain tissue samples were collected 2 h after acute or 24 h after chronic stress. TpH2, 5-HTT and 5-HT1A mRNA levels were determined by real-time-PCR; protein levels - by IHC. ANOVA/MANOVA with Fisher's Protected LSD test was applied to detect significant differences among groups at the p

AB - Background: Dysregulation of serotonergic (5-HT) brain system is implicated in a number of neuropsychiatric disorders including depression, anxiety, obsessive-compulsive disorder as well as autism spectrum disorder. Vulnerability to anxiety and affective disorders in adulthood is dramatically increased after early-life stressful experience. Adverse early-life conditions are accompanied by an increase of glucocorticoid hormones. As we have shown previously, administration of dexamethasone (DEX), a specific synthetic glucocorticoid receptors agonist, reduced the neuronal tryptophan hydroxylase (TpH2) expression, the rate-limiting enzyme for 5-HT synthesis, in the midbrain of the neonatal rats [1]. Here, we tested the hypothesis that overexposure to DEX during neonatal development has programming effects on the brain, resulting in altered behaviors and TpH2 expression in adulthood. Methods: Dexamethasone (DEX) was subcutaneously administered in the therapeutic dose range (0.2 mg/kg) to male rat pups on 3rd day of life (PD3). Control groups were consisting of intact and saline-treated pups. A within-litter design was used to minimize variation in maternal care. After weaning (PD25), animals were kept in litters up to behavioral tests. A protocol of chronic unpredictable mild stress (CUMS) for 15 consecutive days (from PD45 to PD60) during which the presentation of stressors such as bright light, food deprivation, short restriction, hot air, among others, were made. Force swim test (FST) on PD60 was used as acute stress. All animals were also tested for anxiety-like behavior in elevated plus-maze (EPM) on PD52. Brain tissue samples were collected 2 h after acute or 24 h after chronic stress. TpH2, 5-HTT and 5-HT1A mRNA levels were determined by real-time-PCR; protein levels - by IHC. ANOVA/MANOVA with Fisher's Protected LSD test was applied to detect significant differences among groups at the p

UR - https://www.mendeley.com/catalogue/b25fd015-d12e-36de-9ca3-668dd170ed94/

U2 - 10.1016/j.euroneuro.2018.11.361

DO - 10.1016/j.euroneuro.2018.11.361

M3 - Meeting Abstract

VL - 29

SP - S222-S222

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

T2 - 31st Congress of the European-College-of-Neuropsychopharmacology (ECNP)

Y2 - 6 October 2018 through 9 October 2018

ER -