Effects of handling during the postnatal period on the development of brain and behavior of BALB/c mice

Haiyan Li, Chihiro Ishikawa, Tomoyuki Masuda, Takashi Shiga
Kansei, Behavioral and Brain Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan

Development of brain and behavior in mammals is influenced by the interaction of genetic and environmental factors. Mother-to-child relationship is an important environmental factor during the postnatal period, affecting the development of brain and behavior. Postnatal handling, a manipulation that briefly separates offspring from their mother once a day during the postnatal period, has been reported to decrease the stress responsiveness. However, the brain mechanisms remain to be examined. Serotonin (5-HT) is a monoamine which acts as a neurotransmitter in the adult brain. In the developing stages, 5-HT has a neurotrophic activity to regulate the brain development. The abnormalities of 5-HT, 5-HT receptors and transporter have been shown to be associated with developmental disorders. In this study, we examined effects of postnatal handling on the development of brain and behavior of BALB/c mice. Pups were separated from their mother for 15 minutes once a day during the first two weeks of life. At postnatal week 9, we measured anxiety and depression-like behavior, spatial learning and memory, and pain sensitivity by elevated plus maze and forced swim test, Morris water maze, and hot plate test, respectively. Mice were decapitated and their frontal cortex, hippocampus and midbrain included the raphe nuclei were excised to measure the mRNA expression of 5-HT receptors (1A, 2A and 2C) and Brain-derived neurotrophic factor (BDNF) by quantitative RT-PCR. Their anxiety-like behavior was decreased and the ability of learning and memory was improved. Concomitantly with their behavioral changes, the mRNA expression of BDNF in the hippocampus and of 5-HT1A receptor in the midbrain was increased. These studies suggest that increased mRNA expression of BDNF in the hippocampus may be involved both in the improved learning and memory and the lowered anxiety, and that increased mRNA expression of 5-HT1A auto-receptor in the midbrain may be involved in the lowered anxiety.