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Neurexin 1 (NRXN1) Splice Isoform Expression During Human Neocortical Development and Aging

Neurexin 1 (NRXN1), a presynaptic adhesion molecule, is implicated in several neurodevelopmental disorders characterized by synaptic dysfunction including, autism, intellectual disability, and schizophrenia. To gain insight into NRXN1’s involvement in human cortical development we used quantitative...

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Autores principales: Jenkins, Aaron K., Paterson, Clare, Wang, Yanhong, Hyde, Thomas M., Kleinman, Joel E., Law, Amanda J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731316/
https://www.ncbi.nlm.nih.gov/pubmed/26216298
http://dx.doi.org/10.1038/mp.2015.107
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author Jenkins, Aaron K.
Paterson, Clare
Wang, Yanhong
Hyde, Thomas M.
Kleinman, Joel E.
Law, Amanda J.
author_facet Jenkins, Aaron K.
Paterson, Clare
Wang, Yanhong
Hyde, Thomas M.
Kleinman, Joel E.
Law, Amanda J.
author_sort Jenkins, Aaron K.
collection PubMed
description Neurexin 1 (NRXN1), a presynaptic adhesion molecule, is implicated in several neurodevelopmental disorders characterized by synaptic dysfunction including, autism, intellectual disability, and schizophrenia. To gain insight into NRXN1’s involvement in human cortical development we used quantitative real time PCR to examine the expression trajectories of NRXN1, and its predominant isoforms NRXN1-α and NRXN1-β in prefrontal cortex from fetal stages to aging. Additionally, we investigated whether prefrontal cortical expression levels of NRXN1 transcripts are altered in schizophrenia or bipolar disorder in comparison to non-psychiatric control subjects. We observed that all three NRXN1 transcripts were highly expressed during human fetal cortical development, dramatically increasing with gestational age. In the postnatal DLPFC, expression levels were negatively correlated with age, peaking at birth until approximately 3 years of age, after which levels declined dramatically to be stable across the lifespan. NRXN1-β expression was modestly but significantly elevated in the brains of patients with schizophrenia compared to non-psychiatric controls, whereas NRXN1-α expression was increased in bipolar disorder. These data provide novel evidence that NRXN1 expression is highest in human prefrontal cortex during critical developmental windows relevant to the onset and diagnosis of a range of neurodevelopmental disorders, and that NRXN1 expression may be differentially altered in neuropsychiatric disorders.
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spelling pubmed-47313162016-05-18 Neurexin 1 (NRXN1) Splice Isoform Expression During Human Neocortical Development and Aging Jenkins, Aaron K. Paterson, Clare Wang, Yanhong Hyde, Thomas M. Kleinman, Joel E. Law, Amanda J. Mol Psychiatry Article Neurexin 1 (NRXN1), a presynaptic adhesion molecule, is implicated in several neurodevelopmental disorders characterized by synaptic dysfunction including, autism, intellectual disability, and schizophrenia. To gain insight into NRXN1’s involvement in human cortical development we used quantitative real time PCR to examine the expression trajectories of NRXN1, and its predominant isoforms NRXN1-α and NRXN1-β in prefrontal cortex from fetal stages to aging. Additionally, we investigated whether prefrontal cortical expression levels of NRXN1 transcripts are altered in schizophrenia or bipolar disorder in comparison to non-psychiatric control subjects. We observed that all three NRXN1 transcripts were highly expressed during human fetal cortical development, dramatically increasing with gestational age. In the postnatal DLPFC, expression levels were negatively correlated with age, peaking at birth until approximately 3 years of age, after which levels declined dramatically to be stable across the lifespan. NRXN1-β expression was modestly but significantly elevated in the brains of patients with schizophrenia compared to non-psychiatric controls, whereas NRXN1-α expression was increased in bipolar disorder. These data provide novel evidence that NRXN1 expression is highest in human prefrontal cortex during critical developmental windows relevant to the onset and diagnosis of a range of neurodevelopmental disorders, and that NRXN1 expression may be differentially altered in neuropsychiatric disorders. 2015-07-28 2016-05 /pmc/articles/PMC4731316/ /pubmed/26216298 http://dx.doi.org/10.1038/mp.2015.107 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Jenkins, Aaron K.
Paterson, Clare
Wang, Yanhong
Hyde, Thomas M.
Kleinman, Joel E.
Law, Amanda J.
Neurexin 1 (NRXN1) Splice Isoform Expression During Human Neocortical Development and Aging
title Neurexin 1 (NRXN1) Splice Isoform Expression During Human Neocortical Development and Aging
title_full Neurexin 1 (NRXN1) Splice Isoform Expression During Human Neocortical Development and Aging
title_fullStr Neurexin 1 (NRXN1) Splice Isoform Expression During Human Neocortical Development and Aging
title_full_unstemmed Neurexin 1 (NRXN1) Splice Isoform Expression During Human Neocortical Development and Aging
title_short Neurexin 1 (NRXN1) Splice Isoform Expression During Human Neocortical Development and Aging
title_sort neurexin 1 (nrxn1) splice isoform expression during human neocortical development and aging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731316/
https://www.ncbi.nlm.nih.gov/pubmed/26216298
http://dx.doi.org/10.1038/mp.2015.107
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