TY - JOUR

T1 - P.0418 Neonatal dexamethasone prevents an increase of pro-inflammatory cytokines expression after stress in the brains of adolescent and young adult rats

AU - Kalinina, T.

AU - Sukhareva, E.

AU - Bulygina, V.

AU - Lanshakov, D.

AU - Dygalo, N.

N1 - Supported by RFBR 19-015-00525.

PY - 2021/12

Y1 - 2021/12

N2 - Purpose: Long-term consequences of neonatal glucocorticoid hormone treatment can lead to numerous deviations in behavior, mental and metabolic disorders. As has become apparent recently, the correct relationship between neurons and glia during early development is actually important for adult brain function, including the stress response. To clarify this issue, we studied the effect of neonatal dexamethasone (nDEX) on the expression of pro-and anti-inflammatory cytokine genes in the brains of juvenile and young adult rats. The aim is based on our previous data about a time-dependent decrease of cytokine expression in newborn rats' brains after a single injection of dexamethasone [1]. Method(s): The mRNA expression levels of pro-inflammatory (IL1b, IL6, and Tnfa) and anti-inflammatory (IL4, IL10, and TgFb1) cytokines in the rat brainstem, hippocampus, and prefrontal cortex were measured by real-time PCR (Taq-man probes) after subcutaneous injection of dexamethasone (0.2 mg/kg) to 3rd-day-old Wistar rat males. Control groups consisted of intact and saline-treated rats. Effects of nDEX were estimated at 25- and 60-day-old rats. ANOVA/MANOVA with Fisher's Protected LSD test was applied to detect significant differences among groups at the p < 0.05 probability level. Result(s): nDEX resulted in long-term attenuation of anxiety. An increase of time spent in open arms of EPM (F(1, 32)=4.82, p=0.03548) and a decrease in the parameters of Marble-burying-test (F(1, 50)=4.5263, p=0.03833) observed at 22-day-old rats. Both an increase of time spent in open arms of EPM (p 0.1) either on the 25th or 60th day of life. Conclusion(s): Thus, it was found that the activation of the noradrenergic system in the critical period of early development by dexamethasone [2] leads to a weakening of the cytokine activity of the brain. This decrease occurs not only in the first hours after hormonal exposure [1] but also has long-term consequences, preventing an increase in the expression of IL6, IL1b, TNFa genes in the brain stem and hippocampus after stress in adolescents and young adult animals. Our data are consistent and confirm the hypothesis put forward by Sugama [3] about the key role of noradrenaline in modulating the activity of microglia under stress. The established patterns can be one of the reasons for the observed changes in behavior accompanying psycho-emotional disorders. Conflict of interest Disclosure statement: Supported by RFBR 19-015-00525.Copyright © 2021

AB - Purpose: Long-term consequences of neonatal glucocorticoid hormone treatment can lead to numerous deviations in behavior, mental and metabolic disorders. As has become apparent recently, the correct relationship between neurons and glia during early development is actually important for adult brain function, including the stress response. To clarify this issue, we studied the effect of neonatal dexamethasone (nDEX) on the expression of pro-and anti-inflammatory cytokine genes in the brains of juvenile and young adult rats. The aim is based on our previous data about a time-dependent decrease of cytokine expression in newborn rats' brains after a single injection of dexamethasone [1]. Method(s): The mRNA expression levels of pro-inflammatory (IL1b, IL6, and Tnfa) and anti-inflammatory (IL4, IL10, and TgFb1) cytokines in the rat brainstem, hippocampus, and prefrontal cortex were measured by real-time PCR (Taq-man probes) after subcutaneous injection of dexamethasone (0.2 mg/kg) to 3rd-day-old Wistar rat males. Control groups consisted of intact and saline-treated rats. Effects of nDEX were estimated at 25- and 60-day-old rats. ANOVA/MANOVA with Fisher's Protected LSD test was applied to detect significant differences among groups at the p < 0.05 probability level. Result(s): nDEX resulted in long-term attenuation of anxiety. An increase of time spent in open arms of EPM (F(1, 32)=4.82, p=0.03548) and a decrease in the parameters of Marble-burying-test (F(1, 50)=4.5263, p=0.03833) observed at 22-day-old rats. Both an increase of time spent in open arms of EPM (p 0.1) either on the 25th or 60th day of life. Conclusion(s): Thus, it was found that the activation of the noradrenergic system in the critical period of early development by dexamethasone [2] leads to a weakening of the cytokine activity of the brain. This decrease occurs not only in the first hours after hormonal exposure [1] but also has long-term consequences, preventing an increase in the expression of IL6, IL1b, TNFa genes in the brain stem and hippocampus after stress in adolescents and young adult animals. Our data are consistent and confirm the hypothesis put forward by Sugama [3] about the key role of noradrenaline in modulating the activity of microglia under stress. The established patterns can be one of the reasons for the observed changes in behavior accompanying psycho-emotional disorders. Conflict of interest Disclosure statement: Supported by RFBR 19-015-00525.Copyright © 2021

UR - https://www.mendeley.com/catalogue/d3ed5c1c-2049-3b28-86c5-b7aca2486299/

U2 - 10.1016/j.euroneuro.2021.10.391

DO - 10.1016/j.euroneuro.2021.10.391

M3 - Meeting Abstract

VL - 53

SP - S303-S304

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

ER -