Knockdown of DISC1 by In Utero Gene Transfer Disturbs Postnatal Dopaminergic Maturation in the Frontal Cortex and Leads to Adult Behavioral Deficits

Minae Niwa, Atsushi Kamiya, Rina Murai, Ken ichiro Kubo, Aaron J. Gruber, Kenji Tomita, Lingling Lu, Shuta Tomisato, Hanna Jaaro-Peled, Saurav Seshadri, Hideki Hiyama, Beverly Huang, Kazuhisa Kohda, Yukihiro Noda, Patricio O'Donnell, Kazunori Nakajima, Akira Sawa, Toshitaka Nabeshima

研究成果: Article

214 引用 (Scopus)

抜粋

Adult brain function and behavior are influenced by neuronal network formation during development. Genetic susceptibility factors for adult psychiatric illnesses, such as Neuregulin-1 and Disrupted-in-Schizophrenia-1 (DISC1), influence adult high brain functions, including cognition and information processing. These factors have roles during neurodevelopment and are likely to cooperate, forming pathways or "signalosomes." Here we report the potential to generate an animal model via in utero gene transfer in order to address an important question of how nonlethal deficits in early development may affect postnatal brain maturation and high brain functions in adulthood, which are impaired in various psychiatric illnesses such as schizophrenia. We show that transient knockdown of DISC1 in the pre- and perinatal stages, specifically in a lineage of pyramidal neurons mainly in the prefrontal cortex, leads to selective abnormalities in postnatal mesocortical dopaminergic maturation and behavioral abnormalities associated with disturbed cortical neurocircuitry after puberty. PaperFlick: {An electronic component is presented}.

元の言語English
ページ(範囲)480-489
ページ数10
ジャーナルNeuron
65
発行部数4
DOI
出版物ステータスPublished - 25-02-2010
外部発表Yes

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

これを引用

Niwa, M., Kamiya, A., Murai, R., Kubo, K. I., Gruber, A. J., Tomita, K., Lu, L., Tomisato, S., Jaaro-Peled, H., Seshadri, S., Hiyama, H., Huang, B., Kohda, K., Noda, Y., O'Donnell, P., Nakajima, K., Sawa, A., & Nabeshima, T. (2010). Knockdown of DISC1 by In Utero Gene Transfer Disturbs Postnatal Dopaminergic Maturation in the Frontal Cortex and Leads to Adult Behavioral Deficits. Neuron, 65(4), 480-489. https://doi.org/10.1016/j.neuron.2010.01.019