TY - JOUR
T1 - Knockdown of DISC1 by In Utero Gene Transfer Disturbs Postnatal Dopaminergic Maturation in the Frontal Cortex and Leads to Adult Behavioral Deficits
AU - Niwa, Minae
AU - Kamiya, Atsushi
AU - Murai, Rina
AU - Kubo, Ken ichiro
AU - Gruber, Aaron J.
AU - Tomita, Kenji
AU - Lu, Lingling
AU - Tomisato, Shuta
AU - Jaaro-Peled, Hanna
AU - Seshadri, Saurav
AU - Hiyama, Hideki
AU - Huang, Beverly
AU - Kohda, Kazuhisa
AU - Noda, Yukihiro
AU - O'Donnell, Patricio
AU - Nakajima, Kazunori
AU - Sawa, Akira
AU - Nabeshima, Toshitaka
N1 - Funding Information:
We thank Dr. Pamela Talalay and Dr. Eva Anton for critical reading and Ms. Yukiko Lema for organizing the manuscript. This work was supported by U.S. Public Heath Service grant MH-069853 (A.S.), Silvio O. Conte Center grants MH-084018 (A.S.) and MH-088753 (A.S.), and foundation grants from Stanley (A.S.), S-R (A.S., A.K.), RUSK (A.S.), and NARSAD (A.S., A.K., H.J.-P.). This work was also supported by grants from JSPS (T.N., K.N., M.N.), MEXT (T.N., K.N.), MARC (T.N.), MHLW (T.N., K.K.), Sumitomo (K.N.), Naito (K.N.), Academic Frontier Project (T.N.), and Takeda (T.N., K.N.).
PY - 2010/2/25
Y1 - 2010/2/25
N2 - 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}.
AB - 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}.
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U2 - 10.1016/j.neuron.2010.01.019
DO - 10.1016/j.neuron.2010.01.019
M3 - Article
C2 - 20188653
AN - SCOPUS:76849102959
VL - 65
SP - 480
EP - 489
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 4
ER -