Identification of transcriptome alterations in the prefrontal cortex, hippocampus, amygdala and hippocampus of suicide victims

Abstract Suicide is one of the leading causes of death globally for all ages, and as such presents a very serious problem for clinicians worldwide. However, the underlying neurobiological pathology remains to a large extent unknown. In order to address this gap, we have carried out a genome-wide inv...

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Autores principales:	Daniela Glavan, Victor Gheorman, Andrei Gresita, Dirk M. Hermann, Ion Udristoiu, Aurel Popa-Wagner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cd90e41e3b0d4d9b8e30ced7c87384ae
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spelling	oai:doaj.org-article:cd90e41e3b0d4d9b8e30ced7c87384ae2021-12-02T15:14:47ZIdentification of transcriptome alterations in the prefrontal cortex, hippocampus, amygdala and hippocampus of suicide victims10.1038/s41598-021-98210-62045-2322https://doaj.org/article/cd90e41e3b0d4d9b8e30ced7c87384ae2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98210-6https://doaj.org/toc/2045-2322Abstract Suicide is one of the leading causes of death globally for all ages, and as such presents a very serious problem for clinicians worldwide. However, the underlying neurobiological pathology remains to a large extent unknown. In order to address this gap, we have carried out a genome-wide investigation of the gene expression in the amygdala, hippocampus, prefrontal cortex and thalamus in post-mortem brain samples obtained from 20 suicide completers and 7 control subjects. By KEGG enrichment analysis indicated we identified novel clusters of downregulated pathways involved in antigen neutralization and autoimmune thyroid disease (amygdala, thalamus), decreased axonal plasticity in the hippocampus. Two upregulated pathways were involved in neuronal death in the hippocampus and olfactory transduction in the thalamus and the prefrontal cortex. Autoimmune thyroid disease pathway was downregulated only in females. Metabolic pathways involved in Notch signaling amino acid metabolism and unsaturated lipid synthesis were thalamus-specific. Suicide-associated changes in the expression of several genes and pseudogenes that point to various functional mechanisms possibly implicated in the pathology of suicide. Two genes (SNORA13 and RNU4-2) involved in RNA processing were common to all brain regions analyzed. Most of the identified gene expression changes were related to region-specific dysregulated manifestation of genetic and epigenetic mechanisms underlying neurodevelopmental disorders (SNORD114-10, SUSd1), motivation, addiction and motor disorders (CHRNA6), long-term depression (RAB3B), stress response, major depression and schizophrenia (GFAP), signal transduction at the neurovascular unit (NEXN) and inhibitory neurotransmission in spatial learning, neural plasticity (CALB2; CLIC6, ENPP1). Some of the differentially expressed genes were brain specific non-coding RNAs involved in the regulation of translation (SNORA13). One, (PARM1) is a potential oncogene and prognostic biomarker for colorectal cancer with no known function in the brain. Disturbed gene expression involved in antigen neutralization, autoimmunity, neural plasticity, stress response, signal transduction at the neurovascular unit, dysregulated nuclear RNA processing and translation and epigenetic imprinting signatures is associated with suicide and point to regulatory non-coding RNAs as potential targets of new drugs development.Daniela GlavanVictor GheormanAndrei GresitaDirk M. HermannIon UdristoiuAurel Popa-WagnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniela Glavan Victor Gheorman Andrei Gresita Dirk M. Hermann Ion Udristoiu Aurel Popa-Wagner Identification of transcriptome alterations in the prefrontal cortex, hippocampus, amygdala and hippocampus of suicide victims
description	Abstract Suicide is one of the leading causes of death globally for all ages, and as such presents a very serious problem for clinicians worldwide. However, the underlying neurobiological pathology remains to a large extent unknown. In order to address this gap, we have carried out a genome-wide investigation of the gene expression in the amygdala, hippocampus, prefrontal cortex and thalamus in post-mortem brain samples obtained from 20 suicide completers and 7 control subjects. By KEGG enrichment analysis indicated we identified novel clusters of downregulated pathways involved in antigen neutralization and autoimmune thyroid disease (amygdala, thalamus), decreased axonal plasticity in the hippocampus. Two upregulated pathways were involved in neuronal death in the hippocampus and olfactory transduction in the thalamus and the prefrontal cortex. Autoimmune thyroid disease pathway was downregulated only in females. Metabolic pathways involved in Notch signaling amino acid metabolism and unsaturated lipid synthesis were thalamus-specific. Suicide-associated changes in the expression of several genes and pseudogenes that point to various functional mechanisms possibly implicated in the pathology of suicide. Two genes (SNORA13 and RNU4-2) involved in RNA processing were common to all brain regions analyzed. Most of the identified gene expression changes were related to region-specific dysregulated manifestation of genetic and epigenetic mechanisms underlying neurodevelopmental disorders (SNORD114-10, SUSd1), motivation, addiction and motor disorders (CHRNA6), long-term depression (RAB3B), stress response, major depression and schizophrenia (GFAP), signal transduction at the neurovascular unit (NEXN) and inhibitory neurotransmission in spatial learning, neural plasticity (CALB2; CLIC6, ENPP1). Some of the differentially expressed genes were brain specific non-coding RNAs involved in the regulation of translation (SNORA13). One, (PARM1) is a potential oncogene and prognostic biomarker for colorectal cancer with no known function in the brain. Disturbed gene expression involved in antigen neutralization, autoimmunity, neural plasticity, stress response, signal transduction at the neurovascular unit, dysregulated nuclear RNA processing and translation and epigenetic imprinting signatures is associated with suicide and point to regulatory non-coding RNAs as potential targets of new drugs development.
format	article
author	Daniela Glavan Victor Gheorman Andrei Gresita Dirk M. Hermann Ion Udristoiu Aurel Popa-Wagner
author_facet	Daniela Glavan Victor Gheorman Andrei Gresita Dirk M. Hermann Ion Udristoiu Aurel Popa-Wagner
author_sort	Daniela Glavan
title	Identification of transcriptome alterations in the prefrontal cortex, hippocampus, amygdala and hippocampus of suicide victims
title_short	Identification of transcriptome alterations in the prefrontal cortex, hippocampus, amygdala and hippocampus of suicide victims
title_full	Identification of transcriptome alterations in the prefrontal cortex, hippocampus, amygdala and hippocampus of suicide victims
title_fullStr	Identification of transcriptome alterations in the prefrontal cortex, hippocampus, amygdala and hippocampus of suicide victims
title_full_unstemmed	Identification of transcriptome alterations in the prefrontal cortex, hippocampus, amygdala and hippocampus of suicide victims
title_sort	identification of transcriptome alterations in the prefrontal cortex, hippocampus, amygdala and hippocampus of suicide victims
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cd90e41e3b0d4d9b8e30ced7c87384ae
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Identification of transcriptome alterations in the prefrontal cortex, hippocampus, amygdala and hippocampus of suicide victims

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