Cargando…
Epigenetic RELN Dysfunction in Schizophrenia and Related Neuropsychiatric Disorders
REELIN (RELN) is a large (420 kDa) glycoprotein that in adulthood is mostly synthesized in GABAergic neurons of corticolimbic structures. Upon secretion in the extracellular matrix (ECM), RELN binds to VLDL, APOE2, and α3β2 Integrin receptors located on dendritic shafts and spines of postsynaptic py...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820443/ https://www.ncbi.nlm.nih.gov/pubmed/27092053 http://dx.doi.org/10.3389/fncel.2016.00089 |
_version_ | 1782425396911800320 |
---|---|
author | Guidotti, Alessandro Grayson, Dennis R. Caruncho, Hector J. |
author_facet | Guidotti, Alessandro Grayson, Dennis R. Caruncho, Hector J. |
author_sort | Guidotti, Alessandro |
collection | PubMed |
description | REELIN (RELN) is a large (420 kDa) glycoprotein that in adulthood is mostly synthesized in GABAergic neurons of corticolimbic structures. Upon secretion in the extracellular matrix (ECM), RELN binds to VLDL, APOE2, and α3β2 Integrin receptors located on dendritic shafts and spines of postsynaptic pyramidal neurons. Reduced levels of RELN expression in the adult brain induce cognitive impairment and dendritic spine density deficits. RELN supplementation recovers these deficits suggesting a trophic action for RELN in synaptic plasticity. We and others have shown that altered RELN expression in schizophrenia (SZ) and bipolar (BP) disorder patients is difficult to reconcile with classical Mendelian genetic disorders and it is instead plausible to associate these disorders with altered epigenetic homeostasis. Support for the contribution of altered epigenetic mechanisms in the down-regulation of RELN expression in corticolimbic structures of psychotic patients includes the concomitant increase of DNA-methyltransferases and the increased levels of the methyl donor S-adenosylmethionine (SAM). It is hypothesized that these conditions lead to RELN promoter hypermethylation and a reduction in RELN protein amounts in psychotic patients. The decreased synthesis and release of RELN from GABAergic corticolimbic neurons could serve as a model to elucidate the epigenetic pathophysiological mechanisms acting at pyramidal neuron dendrites that regulate synaptic plasticity and cognition in psychotic and non-psychotic subjects. |
format | Online Article Text |
id | pubmed-4820443 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48204432016-04-18 Epigenetic RELN Dysfunction in Schizophrenia and Related Neuropsychiatric Disorders Guidotti, Alessandro Grayson, Dennis R. Caruncho, Hector J. Front Cell Neurosci Neuroscience REELIN (RELN) is a large (420 kDa) glycoprotein that in adulthood is mostly synthesized in GABAergic neurons of corticolimbic structures. Upon secretion in the extracellular matrix (ECM), RELN binds to VLDL, APOE2, and α3β2 Integrin receptors located on dendritic shafts and spines of postsynaptic pyramidal neurons. Reduced levels of RELN expression in the adult brain induce cognitive impairment and dendritic spine density deficits. RELN supplementation recovers these deficits suggesting a trophic action for RELN in synaptic plasticity. We and others have shown that altered RELN expression in schizophrenia (SZ) and bipolar (BP) disorder patients is difficult to reconcile with classical Mendelian genetic disorders and it is instead plausible to associate these disorders with altered epigenetic homeostasis. Support for the contribution of altered epigenetic mechanisms in the down-regulation of RELN expression in corticolimbic structures of psychotic patients includes the concomitant increase of DNA-methyltransferases and the increased levels of the methyl donor S-adenosylmethionine (SAM). It is hypothesized that these conditions lead to RELN promoter hypermethylation and a reduction in RELN protein amounts in psychotic patients. The decreased synthesis and release of RELN from GABAergic corticolimbic neurons could serve as a model to elucidate the epigenetic pathophysiological mechanisms acting at pyramidal neuron dendrites that regulate synaptic plasticity and cognition in psychotic and non-psychotic subjects. Frontiers Media S.A. 2016-04-05 /pmc/articles/PMC4820443/ /pubmed/27092053 http://dx.doi.org/10.3389/fncel.2016.00089 Text en Copyright © 2016 Guidotti, Grayson and Caruncho. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Guidotti, Alessandro Grayson, Dennis R. Caruncho, Hector J. Epigenetic RELN Dysfunction in Schizophrenia and Related Neuropsychiatric Disorders |
title | Epigenetic RELN Dysfunction in Schizophrenia and Related Neuropsychiatric Disorders |
title_full | Epigenetic RELN Dysfunction in Schizophrenia and Related Neuropsychiatric Disorders |
title_fullStr | Epigenetic RELN Dysfunction in Schizophrenia and Related Neuropsychiatric Disorders |
title_full_unstemmed | Epigenetic RELN Dysfunction in Schizophrenia and Related Neuropsychiatric Disorders |
title_short | Epigenetic RELN Dysfunction in Schizophrenia and Related Neuropsychiatric Disorders |
title_sort | epigenetic reln dysfunction in schizophrenia and related neuropsychiatric disorders |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820443/ https://www.ncbi.nlm.nih.gov/pubmed/27092053 http://dx.doi.org/10.3389/fncel.2016.00089 |
work_keys_str_mv | AT guidottialessandro epigeneticrelndysfunctioninschizophreniaandrelatedneuropsychiatricdisorders AT graysondennisr epigeneticrelndysfunctioninschizophreniaandrelatedneuropsychiatricdisorders AT carunchohectorj epigeneticrelndysfunctioninschizophreniaandrelatedneuropsychiatricdisorders |