Ts1Cje Down syndrome model mice exhibit environmental stimuli-triggered locomotor hyperactivity and sociability concurrent with increased flux through central dopamine and serotonin metabolism

Atsushi Shimohata, Keiichi Ishihara, Satoko Hattori, Hiroyuki Miyamoto, Hiromasa Morishita, Guy Ornthanalai, Matthieu Raveau, Abdul Shukkur Ebrahim, Kenji Amano, Kazuyuki Yamada, Haruhiko Sago, Satoshi Akiba, Nobuko Mataga, Niall P. Murphy, Tsuyoshi Miyakawa, Kazuhiro Yamakawa

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Abstract

Ts1Cje mice have a segmental trisomy of chromosome 16 that is orthologous to human chromosome 21 and display Down syndrome-like cognitive impairments. Despite the occurrence of affective and emotional impairments in patients with Down syndrome, these parameters are poorly documented in Down syndrome mouse models, including Ts1Cje mice. Here, we conducted comprehensive behavioral analyses, including anxiety-, sociability-, and depression-related tasks, and biochemical analyses of monoamines and their metabolites in Ts1Cje mice. Ts1Cje mice showed enhanced locomotor activity in novel environments and increased social contact with unfamiliar partners when compared with wild-type littermates, but a significantly lower activity in familiar environments. Ts1Cje mice also exhibited some signs of decreased depression like-behavior. Furthermore, Ts1Cje mice showed monoamine abnormalities, including increased extracellular dopamine and serotonin, and enhanced catabolism in the striatum and ventral forebrain. This study constitutes the first report of deviated monoamine metabolism that may help explain the basis for abnormal behaviors, including the environmental stimuli-triggered hyperactivity, increased sociability and decreased depression-like behavior in Ts1Cje mice.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalExperimental Neurology
Volume293
DOIs
Publication statusPublished - 01-07-2017

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All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience

Cite this

Shimohata, A., Ishihara, K., Hattori, S., Miyamoto, H., Morishita, H., Ornthanalai, G., Raveau, M., Ebrahim, A. S., Amano, K., Yamada, K., Sago, H., Akiba, S., Mataga, N., Murphy, N. P., Miyakawa, T., & Yamakawa, K. (2017). Ts1Cje Down syndrome model mice exhibit environmental stimuli-triggered locomotor hyperactivity and sociability concurrent with increased flux through central dopamine and serotonin metabolism. Experimental Neurology, 293, 1-12. https://doi.org/10.1016/j.expneurol.2017.03.009