The interaction between early life epilepsy and autistic-like behavioral consequences: a role for the mammalian target of rapamycin (mTOR) pathway.

PloS One
Delia M TalosF E Jensen

Abstract

Early life seizures can result in chronic epilepsy, cognitive deficits and behavioral changes such as autism, and conversely epilepsy is common in autistic children. We hypothesized that during early brain development, seizures could alter regulators of synaptic development and underlie the interaction between epilepsy and autism. The mammalian Target of Rapamycin (mTOR) modulates protein translation and is dysregulated in Tuberous Sclerosis Complex, a disorder characterized by epilepsy and autism. We used a rodent model of acute hypoxia-induced neonatal seizures that results in long term increases in neuronal excitability, seizure susceptibility, and spontaneous seizures, to determine how seizures alter mTOR Complex 1 (mTORC1) signaling. We hypothesized that seizures occurring at a developmental stage coinciding with a critical period of synaptogenesis will activate mTORC1, contributing to epileptic networks and autistic-like behavior in later life. Here we show that in the rat, baseline mTORC1 activation peaks during the first three postnatal weeks, and induction of seizures at postnatal day 10 results in further transient activation of its downstream targets phospho-4E-BP1 (Thr37/46), phospho-p70S6K (Thr389) and phospho-S6 (...Continue Reading

References

Jun 1, 1991·Annals of Neurology·F E JensenJ L Burchfiel
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·A E WestM E Greenberg
Jan 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Shao Jun TangErin M Schuman
May 23, 2002·Brain : a Journal of Neurology·Patrick F BoltonAndrew Pickles
Nov 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Maurizio CammalleriPietro Paolo Sanna
Aug 20, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gerhard M SchrattMichael E Greenberg
Sep 29, 2004·Neuron·Raymond J KelleherSusumu Tonegawa
Nov 5, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nobuyuki TakeiHiroyuki Nawa
Nov 10, 2004·The Journal of Cell Biology·Brendan D Manning
Nov 19, 2004·Human Molecular Genetics·Paolo MorettiHuda Y Zoghbi
Jun 9, 2005·Brain Research. Developmental Brain Research·Mohamad A MikatiMarwan El Sabban
Nov 16, 2005·Nature Neuroscience·Sohail F TavazoieBernardo L Sabatini
Dec 13, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Vikas KumarGang-Yi Wu
Apr 15, 2006·The Journal of Biological Chemistry·Aleksandra StojanovicXiaoping Du
May 6, 2006·Neuron·Chang-Hyuk KwonLuis F Parada
May 23, 2006·Gene Expression Patterns : GEP·M J WebsterC Shannon Weickert
Aug 11, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sonja Y GroomsR Suzanne Zukin
Sep 15, 2006·Behavioural Brain Research·Sheryl S MoyJacqueline N Crawley
Oct 17, 2006·Oncogene·J H Reiling, D M Sabatini
Jan 4, 2007·Neurology·Elisabeth B WinterkornElizabeth A Thiele
Feb 20, 2007·Molecular Neurobiology·Jacek Jaworski, Morgan Sheng
May 25, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lynsey MeikleDavid J Kwiatkowski
Jun 1, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Panayiotis TsokasRobert D Blitzer
Jul 7, 2007·Neurobiology of Learning and Memory·Pierre TrifilieffJacques Micheau
Oct 5, 2007·Biochimica Et Biophysica Acta·Lukasz SwiechJacek Jaworski
Nov 7, 2007·Neurology·Gabriel M RonenDavid L Streiner
Dec 1, 2007·Epilepsy Currents·Samuel Wiebe, Dale C Hesdorffer
Apr 5, 2008·Annals of Neurology·Ling-Hui ZengMichael Wong
Apr 29, 2008·Behavioural Brain Research·Sheryl S MoyTerry R Magnuson
May 23, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lynsey MeikleDavid J Kwiatkowski
Jun 24, 2008·Nature Medicine·Dan EhningerAlcino J Silva
Aug 8, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sanjay N RakhadeFrances E Jensen
Oct 28, 2008·Neoplasia : an International Journal for Oncology Research·Abraham SchneiderJ Silvio Gutkind

❮ Previous
Next ❯

Citations

Apr 27, 2013·Future Neurology·Michael Wong
Dec 4, 2013·Brain Research Bulletin·Jessica A BurketStephen I Deutsch
Nov 10, 2013·Nature Reviews. Neuroscience·Eric HanseIlse Riebe
Dec 4, 2012·International Journal of Molecular Sciences·Kenneth MaieseYan Chen Shang
Mar 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Hongyu SunFrances E Jensen
Sep 21, 2013·Italian Journal of Pediatrics·Romina MoaveroPaolo Curatolo
Nov 10, 2012·Pediatric Research·Delia M TalosFrances E Jensen
Nov 9, 2012·Nature Medicine·Annamaria Vezzani
Feb 13, 2013·Current Opinion in Neurology·Roberto Tuchman
Jun 7, 2013·Expert Review of Neurotherapeutics·Paolo Curatolo, Romina Moavero
Jun 7, 2013·Expert Review of Neurotherapeutics·Michael Wong
Jun 23, 2016·Epilepsy & Behavior Case Reports·Romina MoaveroPaolo Curatolo
Oct 6, 2015·Journal of Neuroscience Methods·Hongyu SunFrances E Jensen
Feb 16, 2013·Biochemical and Biophysical Research Communications·Benjamin Y KleinMartha G Welch
Sep 18, 2012·Progress in Neurobiology·Zhao Zhong ChongKenneth Maiese
Jun 15, 2012·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Paolo CuratoloUNKNOWN TSC Consensus Meeting for SEGA and Epilepsy Management
Jun 12, 2014·Journal of Neuropathology and Experimental Neurology·Anand M IyerEleonora Aronica
Oct 16, 2014·Neurobiology of Disease·John J McMahonYunfei Huang
Feb 9, 2016·Expert Review of Neurotherapeutics·Anna Jeong, Michael Wong
Dec 5, 2015·Frontiers in Pediatrics·Seok Kyu Kang, Shilpa D Kadam
Dec 5, 2012·Developmental Medicine and Child Neurology·Agnies M van EeghenElizabeth A Thiele
Sep 17, 2013·Annals of Neurology·Jonathan D Picker, Christopher A Walsh
Mar 21, 2016·Experimental Neurology·Michael S HesterSteve C Danzer
Apr 7, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Rita CitraroGiovambattista De Sarro
Jun 19, 2013·Journal of the Neurological Sciences·Xiang-Fei MengLan Tan
May 31, 2014·Neurobiology of Disease·Ozlem AkmanAristea S Galanopoulou
Sep 1, 2015·Epilepsy Currents·Carl E Stafstrom, Tim A Benke
May 20, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Peter E DavisMustafa Sahin
Jul 19, 2014·Molecular Neurobiology·Liang WangXuefeng Wang
Feb 24, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Jessica A BurketStephen I Deutsch
May 3, 2015·Pharmacological Reports : PR·Krzysztof SadowskiSergiusz Jóźwiak

❮ Previous
Next ❯

Methods Mentioned

BETA
Confocal microscopy
protein assay

Software Mentioned

NIS
Image Reader
maze
ANY
Elements BR
Clampfit
pClamp
Image Gauge

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Barrel cortex

Here is the latest research on barrel cortex, a region of somatosensory and motor corticies in the brain, which are used by animals that rely on whiskers for world exploration.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

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.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

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.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Brain developing: Influences & Outcomes

This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.