Maternal nicotine intoxication before pregnancy induces depressive- and anxiety-like behaviors as well as cognitive deficits in male offspring and correlates with neurobiological changes.

introductionMaternal nicotine use has been suggested to affect the behavior of children and is linked to changes in neurological systems; however, the specific mechanism is yet to be understood.

methodsMice were used to establish a maternal nicotine intoxication model. At postnatal day 60 (adolescent stage), male offspring were tested for behavioral tasks including sucrose preference, open field, elevated plus maze, light/dark box, object recognition, Morris water maze (MWM), and forced swimming. Enzyme-linked immunoassays were used to measure plasma concentrations of neurotransmitters including norepinephrine, dopamine, serotonin, and corticosterone. Serotonin transporter (Sert), brain-derived neurotrophic factor (Bdnf), cAMP response element binding protein (Creb), and phosphorylated (p)Creb mRNA levels were measured using quantitative real-time polymerase chain reaction.

resultsMale offspring of nicotine-intoxicated dams had significantly reduced sucrose preference, mobility time in the forced swimming test, and locomotor and exploratory activities. Offspring in the maternal nicotine intoxication group showed increased signs of depressive- and anxiety-like behavior. Recognition memory in the MWM was compromised in these animals. The hippocampal and prefrontal cortical regions showed significant changes in Bdnf, pCreb, and Sert gene expression, whereas CREB mRNA levels were unaffected. Moreover, compared to the controls, neurogenesis and neuronal viability were also reduced in these animals.

conclusionPrenatal nicotine exposure might affect the hypothalamic-pituitary-adrenal axis and reduce neurogenesis, potentially leading to depressive-like behaviors and cognitive deficiencies in male offspring.