Motor and learning dysfunction during postnatal development in mice defective in dopamine neuronal transmission

Kazuhiro Nishii, Natsuki Matsushita, Hirohide Sawada, Hiromi Sano, Yukihiro Noda, Takayoshi Mamiya, Toshitaka Nabeshima, Ikuko Nagatsu, Tadayoshi Hata, Kazutoshi Kiuchi, Hideo Yoshizato, Kunio Nakashima, Toshiharu Nagatsu, Kazuto Kobayashi

研究成果: Article

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Mice lacking expression of tyrosine hydroxylase (TH), the first and rate-limiting enzyme of the catecholamine biosynthetic pathway, in dopaminergic neuronal cell types were generated by a transgenic rescue approach to clarify the role of dopamine signaling during postnatal development. Introduction of the TH transgene directed by the dopamine β- hydroxylase gene promoter into TH knockout mice restored noradrenaline and adrenaline synthesis, preventing perinatal lethality and cardiac dysfunction in the knockout mice. Lack of TH expression in the cells that normally express the dopaminergic phenotype resulted in a marked reduction of dopamine accumulation in the tissues, which led to multiple behavioral abnormalities at the juvenile stage. These abnormalities were characterized by a reduction in spontaneous locomotor activity, blockade of methamphetamine-induced hyperactivity, cataleptic behavior, and defects in active avoidance learning. In contrast, development of the pituitary gland as well as production and secretion of the pituitary peptide hormones dependent on hypothalamic dopaminergic control were normally maintained, despite defective dopamine synthesis. These results demonstrate that dopamine neurotransmission is essential for controlling spontaneous and voluntary movement and associative learning during postnatal development through the nigrostriatal and mesocorticolimbic pathways.

元の言語English
ページ(範囲)450-464
ページ数15
ジャーナルJournal of Neuroscience Research
54
発行部数4
DOI
出版物ステータスPublished - 15-11-1998

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All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

これを引用

Nishii, K., Matsushita, N., Sawada, H., Sano, H., Noda, Y., Mamiya, T., Nabeshima, T., Nagatsu, I., Hata, T., Kiuchi, K., Yoshizato, H., Nakashima, K., Nagatsu, T., & Kobayashi, K. (1998). Motor and learning dysfunction during postnatal development in mice defective in dopamine neuronal transmission. Journal of Neuroscience Research, 54(4), 450-464. https://doi.org/10.1002/(SICI)1097-4547(19981115)54:4<450::AID-JNR3>3.0.CO;2-B