Effect of the interaction between the serotonin transporter gene and maternal environment on developing mouse brain

Abstract

A number of studies have demonstrated that the common polymorphism in the serotonin transporter gene (5-HTT-LPR) moderates the increased risk for major depression seen in persons exposed to early adverse experiences. Several mouse models of this interaction have been recently established to investigate the increased vulnerability of individuals carrying the 5-HTT-LPR S allele to both early and adult life stressful events. Identifying the immediate effects of an adverse early environment on genetically susceptible individuals is critical to develop effective prevention of its long-term negative consequences of such an interaction. For this purpose we investigated molecular and neurochemical effects promoted by variable amount of maternal care in the brain of developing (postnatal day 10) wild type and heterozygous serotonin transporter knockout mice. Pups experiencing low level of maternal care showed increased levels of brain-derived neurotrophic factor (BDNF) messenger RNA within the hippocampus and primary somato-sensory cortex, and increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor binding in hippocampus in comparison with pups experiencing high level of maternal care. Strikingly, only heterozygous serotonin transporter knockout pups experiencing high maternal care showed increased hippocampal levels of serotonin and norepinephrine and decreased serotonin turnover compared to wild-type littermates. These findings support the hypothesis that maternal care affects the development of the hippocampus and primary somato-sensory cortex of individuals characterized by genetic variants of the serotonin transporter.