MTOR Inhibition Ameliorates Cognitive and Affective Deficits Caused by Disc1 Knockdown in Adult-Born Dentate Granule Neurons

Miou Zhou, Weidong Li, Shan Huang, Juan Song, Ju Young Kim, Xiaoli Tian, Eunchai Kang, Yoshitake Sano, Cindy Liu, J. Balaji, Shumin Wu, Yu Zhou, Ying Zhou, Sherveen N. Parivash, Dan Ehninger, Lin He, Hongjun Song, Guo li Ming, Alcino J. Silva

Research output: Contribution to journalArticle

Abstract

Abnormalities during brain development are thought to cause psychiatric illness and other neurodevelopmental disorders. However, developmental processes such as neurogenesis continue in restricted brain regions of adults, and disruptions of these processes could contribute to the phenotypes of neurodevelopmental disorders. As previously reported, we show that . Disc1 knockdown specifically in adult-born dentate gyrus (DG) neurons results in increased mTOR signaling, hyperexcitability, and neuronal structure deficits. . Disc1 knockdown also resulted in pronounced cognitive and affective deficits, which could be reversed when the affected DG neurons were inactivated. Importantly, reversing increases in mTOR signaling with an FDA-approved inhibitor both prevented and treated these behavioral deficits, even when associated structural deficits were not reversed. Our findings suggest that a component of the affective and cognitive phenotypes in neurodevelopmental disorders may be caused by disruptions in adult-born neurons. Consequently, treatments directed at this cell population may have a significant impact on these phenotypes

Original languageEnglish (US)
Pages (from-to)647-654
Number of pages8
JournalNeuron
Volume77
Issue number4
DOIs
StatePublished - Feb 20 2013

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Dentate Gyrus
Phenotype
Neurons
Neurogenesis
Brain
Psychiatry
Population
Inhibition (Psychology)
Neurodevelopmental Disorders

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

MTOR Inhibition Ameliorates Cognitive and Affective Deficits Caused by Disc1 Knockdown in Adult-Born Dentate Granule Neurons. / Zhou, Miou; Li, Weidong; Huang, Shan; Song, Juan; Kim, Ju Young; Tian, Xiaoli; Kang, Eunchai; Sano, Yoshitake; Liu, Cindy; Balaji, J.; Wu, Shumin; Zhou, Yu; Zhou, Ying; Parivash, Sherveen N.; Ehninger, Dan; He, Lin; Song, Hongjun; Ming, Guo li; Silva, Alcino J.

In: Neuron, Vol. 77, No. 4, 20.02.2013, p. 647-654.

Research output: Contribution to journalArticle

Zhou, M, Li, W, Huang, S, Song, J, Kim, JY, Tian, X, Kang, E, Sano, Y, Liu, C, Balaji, J, Wu, S, Zhou, Y, Zhou, Y, Parivash, SN, Ehninger, D, He, L, Song, H, Ming, GL & Silva, AJ 2013, 'MTOR Inhibition Ameliorates Cognitive and Affective Deficits Caused by Disc1 Knockdown in Adult-Born Dentate Granule Neurons', Neuron, vol. 77, no. 4, pp. 647-654. https://doi.org/10.1016/j.neuron.2012.12.033
Zhou, Miou ; Li, Weidong ; Huang, Shan ; Song, Juan ; Kim, Ju Young ; Tian, Xiaoli ; Kang, Eunchai ; Sano, Yoshitake ; Liu, Cindy ; Balaji, J. ; Wu, Shumin ; Zhou, Yu ; Zhou, Ying ; Parivash, Sherveen N. ; Ehninger, Dan ; He, Lin ; Song, Hongjun ; Ming, Guo li ; Silva, Alcino J. / MTOR Inhibition Ameliorates Cognitive and Affective Deficits Caused by Disc1 Knockdown in Adult-Born Dentate Granule Neurons. In: Neuron. 2013 ; Vol. 77, No. 4. pp. 647-654.
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