Suppression of Akt-mTOR pathway rescued the social behavior in Cntnap2-deficient mice

Scientific Reports
Xiaoliang XingJia-Da Li

Abstract

Autism spectrum disorders (ASD) form a heterogeneous, neurodevelopmental syndrome characterized by deficits in social interactions and repetitive behavior/restricted interests. Dysregulation of mTOR signaling has been implicated in the pathogenesis of certain types of ASD, and inhibition of mTOR by rapamycin has been demonstrated to be an effective therapeutics for impaired social interaction in Tsc1+/-, Tsc2+/-, Pten-/- mice and valproic acid-induced ASD animal models. However, it is still unknown if dysregulation of mTOR signaling is responsible for the ASD-related deficit caused by other genes mutations. Contactin associated protein-like 2 (CNTNAP2) is the first widely replicated autism-predisposition gene. Mice deficient in Cntnap2 (Cntnap2-/- mice) show core ASD-like phenotypes, and have been demonstrated as a validated model for ASD-relevant drug discovery. In this study, we found hyperactive Akt-mTOR signaling in the hippocampus of Cntnap2-/- mice with RNA sequencing followed with biochemical analysis. Treatment with Akt inhibitor LY294002 or mTOR inhibitor rapamycin rescued the social deficit, but had no effect on hyperactivity and repetitive behavior/restricted behavior in Cntnap2-/- mice. We further showed that the ef...Continue Reading

References

Jun 29, 2004·Trends in Neurosciences·Mark F BearStephen T Warren
Jan 9, 2008·American Journal of Human Genetics·Maricela AlarcónDaniel H Geschwind
Jan 9, 2008·American Journal of Human Genetics·Betul BakkalogluMatthew W State
Jun 24, 2009·Current Opinion in Neurobiology·Thomas Bourgeron
Jun 27, 2009·Journal of Medical Genetics·M Neves-PereiraZ Miedzybrodzka
Jun 19, 2010·Nature Reviews. Neuroscience·Jill L SilvermanJacqueline N Crawley
Dec 1, 2010·Trends in Molecular Medicine·Dan Ehninger, Alcino J Silva
Jun 16, 2012·Nature·Michael J SchmeisserTobias M Boeckers
Aug 2, 2012·Genome Biology·Jamee M Berg, Daniel H Geschwind
Oct 18, 2012·Proceedings of the National Academy of Sciences of the United States of America·Garret R AndersonThomas C Südhof
Nov 23, 2012·Nature·Christos G GkogkasNahum Sonenberg
Dec 20, 2012·Nature Communications·Atsushi SatoMasashi Mizuguchi
Jun 8, 2013·BMJ : British Medical Journal·Bob Roehr
Sep 27, 2013·The Journal of Pharmacology and Experimental Therapeutics·John S LazoJoel S Greenberger
Dec 4, 2013·Brain Research Bulletin·Jessica A BurketStephen I Deutsch
Feb 12, 2014·Pediatrics·Tara A LavelleLisa A Prosser
Mar 8, 2014·Frontiers in Cellular Neuroscience·Swati BanerjeeManzoor A Bhat
Nov 5, 2014·Nature·Silvia De RubeisJoseph D Buxbaum
Jan 23, 2015·Science Translational Medicine·Olga PeñagarikanoDaniel H Geschwind
Jan 27, 2015·Nature Neuroscience·Woosuk ChungEunjoon Kim
Apr 29, 2015·Proceedings of the National Academy of Sciences of the United States of America·Olga VareaPeter Penzes
Oct 16, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kimberly M HuberR Suzanne Zukin
Feb 6, 2016·Science·Michael BidinostiIvan Galimberti
Jun 28, 2016·Molecular and Cellular Neurosciences·Liyan QinYunhou Yin
Aug 5, 2017·Science Translational Medicine·Aslihan SelimbeyogluKarl Deisseroth
Jun 15, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Ji-Woon KimChan Young Shin
Nov 6, 2018·Journal of the American Academy of Child and Adolescent Psychiatry·Catherine Lord

❮ Previous
Next ❯

Citations

Nov 21, 2019·Aging·Sabah NisarMohammad Haris
Sep 13, 2020·Autism Research : Official Journal of the International Society for Autism Research·Kaela E ScottBrian L Allman
Jan 21, 2021·Nutrients·Kyoko HasebeMargaret J Morris
Mar 4, 2020·Neuron·Chao TaiLennart Mucke
May 17, 2021·Neurochemistry International·Aarti Sharma, Sidharth Mehan
Nov 3, 2020·European Journal of Pharmacology·Zaiqi ZhangXiao-Liang Xing

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
PCR
protein Assay
reverse transcription PCR
RNA-seq

Software Mentioned

Graph Pad
Anilab
Prism

Related Concepts

Related Feeds

Attention Disorders

Attention is involved in all cognitive activities, and attention disorders are reported in patients with various neurological diseases. Here are the latest discoveries pertaining to attention disorders.

Autism

Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.