Modeling synaptogenesis in schizophrenia and autism using human iPSC derived neurons

Molecular and Cellular Neurosciences
Christa W HabelaGuo-Li Ming


Schizophrenia (SCZ) and autism spectrum disorder (ASD) are genetically and phenotypically complex disorders of neural development. Human genetic studies, as well as studies examining structural changes at the cellular level, have converged on glutamatergic synapse formation, function, and maintenance as common pathophysiologic substrates involved in both disorders. Synapses as basic functional units of the brain are continuously modified by experience throughout life, therefore they are particularly attractive candidates for targeted therapy. Until recently we lacked a system to evaluate dynamic changes that lead to synaptic abnormalities. With the development of techniques to generate induced pluripotent stem cells (iPSCs) from patients, we are now able to study neuronal and synaptic development in cells from individual patients in the context of genetic changes conferring disease susceptibility. In this review, we discuss recent studies focusing on neural cells differentiated from SCZ and ASD patient iPSCs. These studies support a central role for glutamatergic synapse formation and function in both disorders and demonstrate that iPSC derived neurons offer a potential system for further evaluation of processes leading to syna...Continue Reading


Mar 26, 2016·Molecular and Cellular Neurosciences·Rakesh Karmacharya, Stephen J Haggarty
Dec 17, 2016·Journal of Neurodevelopmental Disorders·Vickie KwanKarun K Singh
Apr 19, 2017·Proceedings of the National Academy of Sciences of the United States of America·Georgia KouroupiRebecca Matsas
Oct 3, 2017·Frontiers in Neuroscience·John R KellyTimothy G Dinan
Mar 27, 2018·Developmental Neurobiology·Aditi Deshpande, Lauren A Weiss
Aug 8, 2019·Nature Communications·Abigail U CarbonellBryen A Jordan
Dec 12, 2019·Frontiers in Synaptic Neuroscience·Jorge Ojeda, Ariel Ávila
Dec 2, 2016·Frontiers in Cellular Neuroscience·Yu-Chih LinGene J Blatt
Jan 9, 2019·Frontiers in Pediatrics·Beatriz C FreitasMaria Carolina Marchetto
Feb 9, 2020·Journal of Autism and Developmental Disorders·Paul A ConstableJames C McPartland
May 20, 2020·Frontiers in Psychiatry·Danielle Gouvêa-JunqueiraFernanda Crunfli


May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·T A ComeryW T Greenough
Mar 31, 1998·The British Journal of Psychiatry : the Journal of Mental Science·S Brown
Oct 15, 1998·Journal of Neurology, Neurosurgery, and Psychiatry·L J GareyS R Hirsch
Jan 13, 2000·Archives of General Psychiatry·L A Glantz, D A Lewis
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tyrone D CannonJaakko Kaprio
Jul 23, 2003·Neuron·W Gordon FrankleMarc Laruelle
Dec 10, 2003·Archives of General Psychiatry·Patrick F SullivanMichael C Neale
Jan 18, 2005·Biological Psychiatry·Ruth A Carper, Eric Courchesne
Feb 8, 2005·Progress in Neuro-psychopharmacology & Biological Psychiatry·Jessie S ChambersNora I Perrone-Bizzozero
May 27, 2005·PLoS Medicine·Sukanta SahaJohn McGrath
Jun 3, 2005·The American Journal of Psychiatry·Nutan KolluriDavid A Lewis
Jan 31, 2006·Biological Psychiatry·Paul J Harrison, Amanda J Law
Nov 1, 2006·Journal of Child Psychology and Psychiatry, and Allied Disciplines·Deanna GreensteinNitin Gogtay
May 22, 2007·Nature Reviews. Neuroscience·C Geoffrey Lau, R Suzanne Zukin
Nov 22, 2007·Science·Junying YuJames A Thomson
Dec 15, 2007·Nature Protocols·Kazutoshi TakahashiShinya Yamanaka
Dec 18, 2007·Biological Psychiatry·Daniel C Javitt
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·W E LowryK Plath
Feb 27, 2008·Brain : a Journal of Neurology·Yong LiuTianzi Jiang
May 9, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Robert A SweetDavid A Lewis
May 16, 2008·Epidemiologic Reviews·John McGrathJoy Welham
Oct 22, 2008·Nature Biotechnology·Trond AasenJuan Carlos Izpisúa Belmonte
Nov 11, 2008·Neuron·Thomas C Südhof, Robert C Malenka
Feb 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Daniela TropeaMriganka Sur
Apr 8, 2009·Current Neurology and Neuroscience Reports·Ravinesh A Kumar, Susan L Christian
Oct 13, 2009·Lancet·Susan E LevyRobert T Schultz

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