Impact of maternal desvenlafaxine exposure on brain development in pregnant albino rats and their fetuses

J Biochem Mol Toxicol. 2022 Jul;36(7):e23062. doi: 10.1002/jbt.23062. Epub 2022 Apr 1.

Abstract

Depression during pregnancy adversely affects fetal development. Desvenlafaxine drug is used for the treatment of gestational depression. In light of the well-established role of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in regulating neurogenesis and neural survival, the role of S100b in nerve cell energetic metabolism, differentiation of neurons and glial cells, an aberrant increase in NGF, BDNF and S100b expression in the fetal brain may contribute to desvenlafaxine cognitive disorders by altering brain development. This study is trying to determine the effect of desvenlafaxine on brain development. Thirty timed pregnant rats (from the 5th to the 20th day) were divided into three groups: control, low dose (5.14 mg/kg/day) and high dose (10.28 mg/kg/day) of desvenlafaxine where all animals received the corresponding doses by gavage. Maternal and fetal brain samples were fixed for histological, immunohistochemical (IHC) study of NGF and evaluated for BDNF and S100b genes expression. Desvenlafaxine induced some of the histopathological alterations in maternal and fetal rat brains. Moreover, IHC analysis of maternal and fetal rat brains showed that groups treated with desvenlafaxine demonstrated a significant increase of NGF protein immunoreactivity compared with that in the controls. Gene expression results revealed upregulation of messenger RNA BDNF and S100B expression. According to developmental changes in the brain, desvenlafaxine affects neonatal growth during pregnancy, which may lead to delay of brain development. So, it is essential to survey the roles of antidepressant drugs on neonatal development during pregnancy.

Keywords: Wistar Rat brain; desvenlafaxine; gene expression; gestational period.

MeSH terms

  • Animals
  • Brain* / drug effects
  • Brain* / growth & development
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Desvenlafaxine Succinate* / adverse effects
  • Female
  • Fetus / metabolism
  • Maternal Exposure* / adverse effects
  • Nerve Growth Factor* / metabolism
  • Pregnancy
  • Rats

Substances

  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factor
  • Desvenlafaxine Succinate