PT  - JOURNAL ARTICLE
AU  - Jing Zhou
AU  - Jacqueline Blundell
AU  - Shiori Ogawa
AU  - Chang-Hyuk Kwon
AU  - Wei Zhang
AU  - Christopher Sinton
AU  - Craig M. Powell
AU  - Luis F. Parada
TI  - Pharmacological Inhibition of mTORC1 Suppresses Anatomical, Cellular, and Behavioral Abnormalities in Neural-Specific <em>Pten</em> Knock-Out Mice
AID  - 10.1523/JNEUROSCI.5685-08.2009
DP  - 2009 Feb 11
TA  - The Journal of Neuroscience
PG  - 1773--1783
VI  - 29
IP  - 6
4099  - http://www.jneurosci.org/content/29/6/1773.short
4100  - http://www.jneurosci.org/content/29/6/1773.full
SO  - J. Neurosci.2009 Feb 11; 29
AB  - PTEN (phosphatase and tensin homolog deleted on chromosome ten) is a lipid phosphatase that counteracts the function of phosphatidylinositol-3 kinase (PI3K). Loss of function of PTEN results in constitutive activation of AKT and downstream effectors and correlates with many human cancers, as well as various brain disorders, including macrocephaly, seizures, Lhermitte–Duclos disease, and autism. We previously generated a conditional Pten knock-out mouse line with Pten loss in limited postmitotic neurons in the cortex and hippocampus. Pten-null neurons developed neuronal hypertrophy and loss of neuronal polarity. The mutant mice exhibited macrocephaly and behavioral abnormalities reminiscent of certain features of human autism. Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin complex 1 (mTORC1), can prevent and reverse neuronal hypertrophy, resulting in the amelioration of a subset of PTEN-associated abnormal behaviors, providing evidence that the mTORC1 pathway downstream of PTEN is critical for this complex phenotype.