mTOR Inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons

Miou Zhou, Weidong Li* (Corresponding Author), 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* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)

Abstract

Abnormalities during brain development are thoughtto cause psychiatric illness and other neurodevelopmental disorders. However, developmental processes such as neurogenesis continue in restrictedbrain regions of adults, and disruptions of theseprocesses could contribute to the phenotypes of neurodevelopmental disorders. As previously reported, we show that Disc1 knockdown specificallyin adult-born dentate gyrus (DG) neurons results inincreased mTOR signaling, hyperexcitability, andneuronal structure deficits. Disc1 knockdown also resulted in pronounced cognitive and affective deficits,which could be reversed when the affected DGneurons were inactivated. Importantly, reversingincreases in mTOR signaling with an FDA-approvedinhibitor both prevented and treated these behavioraldeficits, even when associated structural deficitswere not reversed. Our findings suggest thata component of the affective and cognitive phenotypes in neurodevelopmental disorders may becaused by disruptions in adult-born neurons. Consequently, treatments directed at this cell populationmay have a significant impact on these phenotypes
Original languageEnglish
Pages (from-to)647-654
Number of pages8
JournalNeuron
Volume77
Issue number4
DOIs
Publication statusPublished - 20 Feb 2013

Keywords

  • Aging
  • Animals
  • Cognition/physiology
  • Dentate Gyrus/cytology
  • Gene Knockdown Techniques
  • Mice
  • Nerve Tissue Proteins/genetics
  • Neurogenesis/genetics
  • Neurons/cytology
  • Signal Transduction/genetics
  • TOR Serine-Threonine Kinases/antagonists & inhibitors

Fingerprint Dive into the research topics of 'mTOR Inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons'. Together they form a unique fingerprint.

Cite this