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Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex / M. SCHWEDE in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)
[article]
Titre : Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex Type de document : Texte imprimé et/ou numérique Auteurs : M. SCHWEDE, Auteur ; S. NAGPAL, Auteur ; M. J. GANDAL, Auteur ; N. N. PARIKSHAK, Auteur ; K. MIRNICS, Auteur ; D. H. GESCHWIND, Auteur ; E. M. MORROW, Auteur Année de publication : 2018 Article en page(s) : 18 p. Langues : Anglais (eng) Mots-clés : Autism Cortex Human Post-mortem Transcriptome Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic studies in autism have pinpointed a heterogeneous group of loci and genes. Further, environment may be an additional factor conferring susceptibility to autism. Transcriptome studies investigate quantitative differences in gene expression between patient-derived tissues and control. These studies may pinpoint genes relevant to pathophysiology yet circumvent the need to understand genetic architecture or gene-by-environment interactions leading to disease. METHODS: We conducted alternate gene set enrichment analyses using differentially expressed genes from a previously published RNA-seq study of post-mortem autism cerebral cortex. We used three previously published microarray datasets for validation and one of the microarray datasets for additional differential expression analysis. The RNA-seq study used 26 autism and 33 control brains in differential gene expression analysis, and the largest microarray dataset contained 15 autism and 16 control post-mortem brains. RESULTS: While performing a gene set enrichment analysis of genes differentially expressed in the RNA-seq study, we discovered that genes associated with mitochondrial function were downregulated in autism cerebral cortex, as compared to control. These genes were correlated with genes related to synaptic function. We validated these findings across the multiple microarray datasets. We also did separate differential expression and gene set enrichment analyses to confirm the importance of the mitochondrial pathway among downregulated genes in post-mortem autism cerebral cortex. CONCLUSIONS: We found that genes related to mitochondrial function were differentially expressed in autism cerebral cortex and correlated with genes related to synaptic transmission. Our principal findings replicate across all datasets investigated. Further, these findings may potentially replicate in other diseases, such as in schizophrenia. En ligne : http://dx.doi.org/10.1186/s11689-018-9237-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386
in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 18 p.[article] Strong correlation of downregulated genes related to synaptic transmission and mitochondria in post-mortem autism cerebral cortex [Texte imprimé et/ou numérique] / M. SCHWEDE, Auteur ; S. NAGPAL, Auteur ; M. J. GANDAL, Auteur ; N. N. PARIKSHAK, Auteur ; K. MIRNICS, Auteur ; D. H. GESCHWIND, Auteur ; E. M. MORROW, Auteur . - 2018 . - 18 p.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 18 p.
Mots-clés : Autism Cortex Human Post-mortem Transcriptome Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic studies in autism have pinpointed a heterogeneous group of loci and genes. Further, environment may be an additional factor conferring susceptibility to autism. Transcriptome studies investigate quantitative differences in gene expression between patient-derived tissues and control. These studies may pinpoint genes relevant to pathophysiology yet circumvent the need to understand genetic architecture or gene-by-environment interactions leading to disease. METHODS: We conducted alternate gene set enrichment analyses using differentially expressed genes from a previously published RNA-seq study of post-mortem autism cerebral cortex. We used three previously published microarray datasets for validation and one of the microarray datasets for additional differential expression analysis. The RNA-seq study used 26 autism and 33 control brains in differential gene expression analysis, and the largest microarray dataset contained 15 autism and 16 control post-mortem brains. RESULTS: While performing a gene set enrichment analysis of genes differentially expressed in the RNA-seq study, we discovered that genes associated with mitochondrial function were downregulated in autism cerebral cortex, as compared to control. These genes were correlated with genes related to synaptic function. We validated these findings across the multiple microarray datasets. We also did separate differential expression and gene set enrichment analyses to confirm the importance of the mitochondrial pathway among downregulated genes in post-mortem autism cerebral cortex. CONCLUSIONS: We found that genes related to mitochondrial function were differentially expressed in autism cerebral cortex and correlated with genes related to synaptic transmission. Our principal findings replicate across all datasets investigated. Further, these findings may potentially replicate in other diseases, such as in schizophrenia. En ligne : http://dx.doi.org/10.1186/s11689-018-9237-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 Decreased parvalbumin mRNA levels in cerebellar Purkinje cells in autism / Jean-Jacques SOGHOMONIAN in Autism Research, 10-11 (November 2017)
[article]
Titre : Decreased parvalbumin mRNA levels in cerebellar Purkinje cells in autism Type de document : Texte imprimé et/ou numérique Auteurs : Jean-Jacques SOGHOMONIAN, Auteur ; Kunzhong ZHANG, Auteur ; Sujithra REPRAKASH, Auteur ; Gene J. BLATT, Auteur Article en page(s) : p.1787-1796 Langues : Anglais (eng) Mots-clés : post-mortem parvalbumin cerebellum GABA gene expression Index. décimale : PER Périodiques Résumé : Recent neuropathology studies in human brains indicate that several areas of the prefrontal cortex have decreased numbers of parvalbumin interneurons or decreased parvalbumin expression in Autism Spectrum disorders (ASD) [Hashemi, Ariza, Rogers, Noctor, & Martinez-Cerdeno, 2017; Zikopoulos & Barbas, ]. These data suggest that a deficit in parvalbumin may be a key neuropathology of ASD and contribute to altered GABAergic inhibition. However, it is unclear if a deficit in parvalbumin is a phenomenon that occurs in regions other than the cerebral cortex. The cerebellum is a major region where neuropathology was first detected in ASD over three decades ago [Bauman & Kemper, ]. In view of the documented association between parvalbumin-expressing neurons and autism, the objective of the present study was to determine if parvalbumin gene expression is also altered in Purkinje neurons of the cerebellum. Radioisotopic in situ hybridization histochemistry was used on human tissue sections from control and ASD brains in order to detect and measure parvalbumin mRNA levels at the single cell level in Purkinje cells of Crus II of the lateral cerebellar hemispheres. Results indicate that parvalbumin mRNA levels are significantly lower in Purkinje cells in ASD compared to control brains. This decrease was not influenced by post-mortem interval or age at death. This result indicates that decreased parvalbumin expression is a more widespread feature of ASD. We discuss how this decrease may be implicated in altered cerebellar output to the cerebral cortex and in key ASD symptoms. Autism Res 2017, 10: 1787–1796. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary The cerebellum of the brain controls movement and cognition, including memory and language. This study investigated mechanisms of cerebellar function in Autism. Our hypothesis is that parvalbumin, a molecule that controls and coordinate many cellular brain functions, contributes to the excitatory/inhibitory imbalance in Autism. We report that parvalbumin expression is depressed in Purkinje cells of the cerebellum in autism. This finding contributes to elucidate the cellular and molecular underpinings of autism and should provide a direction for future therapies. En ligne : http://dx.doi.org/10.1002/aur.1835 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=322
in Autism Research > 10-11 (November 2017) . - p.1787-1796[article] Decreased parvalbumin mRNA levels in cerebellar Purkinje cells in autism [Texte imprimé et/ou numérique] / Jean-Jacques SOGHOMONIAN, Auteur ; Kunzhong ZHANG, Auteur ; Sujithra REPRAKASH, Auteur ; Gene J. BLATT, Auteur . - p.1787-1796.
Langues : Anglais (eng)
in Autism Research > 10-11 (November 2017) . - p.1787-1796
Mots-clés : post-mortem parvalbumin cerebellum GABA gene expression Index. décimale : PER Périodiques Résumé : Recent neuropathology studies in human brains indicate that several areas of the prefrontal cortex have decreased numbers of parvalbumin interneurons or decreased parvalbumin expression in Autism Spectrum disorders (ASD) [Hashemi, Ariza, Rogers, Noctor, & Martinez-Cerdeno, 2017; Zikopoulos & Barbas, ]. These data suggest that a deficit in parvalbumin may be a key neuropathology of ASD and contribute to altered GABAergic inhibition. However, it is unclear if a deficit in parvalbumin is a phenomenon that occurs in regions other than the cerebral cortex. The cerebellum is a major region where neuropathology was first detected in ASD over three decades ago [Bauman & Kemper, ]. In view of the documented association between parvalbumin-expressing neurons and autism, the objective of the present study was to determine if parvalbumin gene expression is also altered in Purkinje neurons of the cerebellum. Radioisotopic in situ hybridization histochemistry was used on human tissue sections from control and ASD brains in order to detect and measure parvalbumin mRNA levels at the single cell level in Purkinje cells of Crus II of the lateral cerebellar hemispheres. Results indicate that parvalbumin mRNA levels are significantly lower in Purkinje cells in ASD compared to control brains. This decrease was not influenced by post-mortem interval or age at death. This result indicates that decreased parvalbumin expression is a more widespread feature of ASD. We discuss how this decrease may be implicated in altered cerebellar output to the cerebral cortex and in key ASD symptoms. Autism Res 2017, 10: 1787–1796. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary The cerebellum of the brain controls movement and cognition, including memory and language. This study investigated mechanisms of cerebellar function in Autism. Our hypothesis is that parvalbumin, a molecule that controls and coordinate many cellular brain functions, contributes to the excitatory/inhibitory imbalance in Autism. We report that parvalbumin expression is depressed in Purkinje cells of the cerebellum in autism. This finding contributes to elucidate the cellular and molecular underpinings of autism and should provide a direction for future therapies. En ligne : http://dx.doi.org/10.1002/aur.1835 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=322