Brain region-specific altered expression and association of mitochondria-related genes in autism / Ayyappan ANITHA in Molecular Autism, (November 2012)  

Public ISBD [article]  inMolecular Autism > (November 2012) . - 12 p. Titre : Brain region-specific altered expression and association of mitochondria-related genes in autism Type de document : Texte imprimé et/ou numérique Auteurs : Ayyappan ANITHA, Auteur ; Kazuhiko NAKAMURA, Auteur ; Ismail THANSEEM, Auteur ; Kazuo YAMADA, Auteur ; Yoshimi IWAYAMA, Auteur ; Tomoko TOYOTA, Auteur ; Hideo MATSUZAKI, Auteur ; Taishi MIYACHI, Auteur ; Satoru YAMADA, Auteur ; Masatsugu TSUJII, Auteur ; Kenji J. TSUCHIYA, Auteur ; Kaori MATSUMOTO, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Hironobu ICHIKAWA, Auteur ; Toshiro SUGIYAMA, Auteur ; Takeo YOSHIKAWA, Auteur ; Norio MORI, Auteur Année de publication : 2012 Article en page(s) : 12 p. Langues : Anglais (eng) Mots-clés : Autism  Mitochondria  Postmortem brain  NEFL  Uncoupling protein  Metaxin Index. décimale : PER Périodiques Résumé : BACKGROUND:Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions.METHODS:For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct ([increment][increment]Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism.RESULTS:Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14, SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism patients.CONCLUSIONS:Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted. En ligne : http://dx.doi.org/10.1186/2040-2392-3-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Brain region-specific altered expression and association of mitochondria-related genes in autism [Texte imprimé et/ou numérique] / Ayyappan ANITHA, Auteur ; Kazuhiko NAKAMURA, Auteur ; Ismail THANSEEM, Auteur ; Kazuo YAMADA, Auteur ; Yoshimi IWAYAMA, Auteur ; Tomoko TOYOTA, Auteur ; Hideo MATSUZAKI, Auteur ; Taishi MIYACHI, Auteur ; Satoru YAMADA, Auteur ; Masatsugu TSUJII, Auteur ; Kenji J. TSUCHIYA, Auteur ; Kaori MATSUMOTO, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Hironobu ICHIKAWA, Auteur ; Toshiro SUGIYAMA, Auteur ; Takeo YOSHIKAWA, Auteur ; Norio MORI, Auteur . - 2012 . - 12 p. Langues : Anglais (eng) in Molecular Autism > (November 2012) . - 12 p. Mots-clés : Autism  Mitochondria  Postmortem brain  NEFL  Uncoupling protein  Metaxin Index. décimale : PER Périodiques Résumé : BACKGROUND:Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions.METHODS:For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct ([increment][increment]Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism.RESULTS:Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14, SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism patients.CONCLUSIONS:Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted. En ligne : http://dx.doi.org/10.1186/2040-2392-3-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism / Shiro SUDA in Molecular Autism, (August 2011)  

Public ISBD [article]  inMolecular Autism > (August 2011) . - 5 p. Titre : Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism Type de document : Texte imprimé et/ou numérique Auteurs : Shiro SUDA, Auteur ; Keiko IWATA, Auteur ; Chie SHIMMURA, Auteur ; Yosuke KAMENO, Auteur ; Ayyappan ANITHA, Auteur ; Ismail THANSEEM, Auteur ; Kazuhiko NAKAMURA, Auteur ; Hideo MATSUZAKI, Auteur ; Kenji J. TSUCHIYA, Auteur ; Genichi SUGIHARA, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Keita KOIZUMI, Auteur ; Haruhiro HIGASHIDA, Auteur ; Nori TAKEI, Auteur ; Norio MORI, Auteur Année de publication : 2011 Article en page(s) : 5 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:Axon-guidance proteins play a crucial role in brain development. As the dysfunction of axon-guidance signaling is thought to underlie the microstructural abnormalities of the brain in people with autism, we examined the postmortem brains of people with autism to identify any changes in the expression of axon-guidance proteins.RESULTS:The mRNA and protein expression of axon-guidance proteins, including ephrin (EFN)A4, eEFNB3, plexin (PLXN)A4, roundabout 2 (ROBO)2 and ROBO3, were examined in the anterior cingulate cortex and primary motor cortex of autistic brains (n = 8 and n = 7, respectively) and control brains (n = 13 and n = 8, respectively) using real-time reverse-transcriptase PCR (RT-PCR) and western blotting. Real-time RT-PCR revealed that the relative expression levels of EFNB3, PLXNA4A and ROBO2 were significantly lower in the autistic group than in the control group. The protein levels of these three genes were further analyzed by western blotting, which showed that the immunoreactive values for PLXNA4 and ROBO2, but not for EFNB3, were significantly reduced in the ACC of the autistic brains compared with control brains.CONCLUSIONS:In this study, we found decreased expression of axon-guidance proteins such as PLXNA4 and ROBO2 in the brains of people with autism, and suggest that dysfunctional axon-guidance protein expression may play an important role in the pathophysiology of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-14 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149 [article] Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism [Texte imprimé et/ou numérique] / Shiro SUDA, Auteur ; Keiko IWATA, Auteur ; Chie SHIMMURA, Auteur ; Yosuke KAMENO, Auteur ; Ayyappan ANITHA, Auteur ; Ismail THANSEEM, Auteur ; Kazuhiko NAKAMURA, Auteur ; Hideo MATSUZAKI, Auteur ; Kenji J. TSUCHIYA, Auteur ; Genichi SUGIHARA, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Keita KOIZUMI, Auteur ; Haruhiro HIGASHIDA, Auteur ; Nori TAKEI, Auteur ; Norio MORI, Auteur . - 2011 . - 5 p. Langues : Anglais (eng) in Molecular Autism > (August 2011) . - 5 p. Index. décimale : PER Périodiques Résumé : BACKGROUND:Axon-guidance proteins play a crucial role in brain development. As the dysfunction of axon-guidance signaling is thought to underlie the microstructural abnormalities of the brain in people with autism, we examined the postmortem brains of people with autism to identify any changes in the expression of axon-guidance proteins.RESULTS:The mRNA and protein expression of axon-guidance proteins, including ephrin (EFN)A4, eEFNB3, plexin (PLXN)A4, roundabout 2 (ROBO)2 and ROBO3, were examined in the anterior cingulate cortex and primary motor cortex of autistic brains (n = 8 and n = 7, respectively) and control brains (n = 13 and n = 8, respectively) using real-time reverse-transcriptase PCR (RT-PCR) and western blotting. Real-time RT-PCR revealed that the relative expression levels of EFNB3, PLXNA4A and ROBO2 were significantly lower in the autistic group than in the control group. The protein levels of these three genes were further analyzed by western blotting, which showed that the immunoreactive values for PLXNA4 and ROBO2, but not for EFNB3, were significantly reduced in the ACC of the autistic brains compared with control brains.CONCLUSIONS:In this study, we found decreased expression of axon-guidance proteins such as PLXNA4 and ROBO2 in the brains of people with autism, and suggest that dysfunctional axon-guidance protein expression may play an important role in the pathophysiology of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-14 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149

Serum microRNA profiles in children with autism / Mahesh MUNDALIL VASU in Molecular Autism, (July 2014)  

Public ISBD [article]  inMolecular Autism > (July 2014) . - p.1-9 Titre : Serum microRNA profiles in children with autism Type de document : Texte imprimé et/ou numérique Auteurs : Mahesh MUNDALIL VASU, Auteur ; Ayyappan ANITHA, Auteur ; Ismail THANSEEM, Auteur ; Katsuaki SUZUKI, Auteur ; Kohei YAMADA, Auteur ; Taro TAKAHASHI, Auteur ; Tomoyasu WAKUDA, Auteur ; Keiko IWATA, Auteur ; Masatsugu TSUJII, Auteur ; Toshirou SUGIYAMA, Auteur ; Norio MORI, Auteur Article en page(s) : p.1-9 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : As regulators of gene expression, microRNAs (miRNAs) play a key role in the transcriptional networks of the developing human brain. Circulating miRNAs in the serum and plasma are remarkably stable and are suggested to have promise as noninvasive biomarkers for neurological and neurodevelopmental disorders. We examined the serum expression profiles of neurologically relevant miRNAs in autism spectrum disorder (ASD), a complex neurodevelopmental disorder characterized by multiple deficits in communication, social interaction and behavior. En ligne : http://dx.doi.org/10.1186/2040-2392-5-40 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276 [article] Serum microRNA profiles in children with autism [Texte imprimé et/ou numérique] / Mahesh MUNDALIL VASU, Auteur ; Ayyappan ANITHA, Auteur ; Ismail THANSEEM, Auteur ; Katsuaki SUZUKI, Auteur ; Kohei YAMADA, Auteur ; Taro TAKAHASHI, Auteur ; Tomoyasu WAKUDA, Auteur ; Keiko IWATA, Auteur ; Masatsugu TSUJII, Auteur ; Toshirou SUGIYAMA, Auteur ; Norio MORI, Auteur . - p.1-9. Langues : Anglais (eng) in Molecular Autism > (July 2014) . - p.1-9 Index. décimale : PER Périodiques Résumé : As regulators of gene expression, microRNAs (miRNAs) play a key role in the transcriptional networks of the developing human brain. Circulating miRNAs in the serum and plasma are remarkably stable and are suggested to have promise as noninvasive biomarkers for neurological and neurodevelopmental disorders. We examined the serum expression profiles of neurologically relevant miRNAs in autism spectrum disorder (ASD), a complex neurodevelopmental disorder characterized by multiple deficits in communication, social interaction and behavior. En ligne : http://dx.doi.org/10.1186/2040-2392-5-40 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276

Vldlr overexpression causes hyperactivity in rats / Keiko IWATA in Molecular Autism, (October 2012)  

Public ISBD [article]  inMolecular Autism > (October 2012) . - 9 p. Titre : Vldlr overexpression causes hyperactivity in rats Type de document : Texte imprimé et/ou numérique Auteurs : Keiko IWATA, Auteur ; Nobuo IZUMO, Auteur ; Hideo MATSUZAKI, Auteur ; Takayuki MANABE, Auteur ; Yukiko ISHIBASHI, Auteur ; Yukio ICHITANI, Auteur ; Kazuo YAMADA, Auteur ; Ismail THANSEEM, Auteur ; Ayyappan ANITHA, Auteur ; Mahesh VASU, Auteur ; Chie SHIMMURA, Auteur ; Tomoyasu WAKUDA, Auteur ; Yosuke KAMENO, Auteur ; Taro TAKAHASHI, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Kazuhiko NAKAMURA, Auteur ; Norio MORI, Auteur Année de publication : 2012 Article en page(s) : 9 p. Langues : Anglais (eng) Mots-clés : Hyperactivity  Neurodevelopmental disorder  Psychiatric disorder  Reelin  Transgenic rat  Vldlr Index. décimale : PER Périodiques Résumé : BACKGROUND:Reelin regulates neuronal positioning in cortical brain structures and neuronal migration via binding to the lipoprotein receptors Vldlr and Lrp8. Reeler mutant mice display severe brain morphological defects and behavioral abnormalities. Several reports have implicated reelin signaling in the etiology of neurodevelopmental and psychiatric disorders, including autism, schizophrenia, bipolar disorder, and depression. Moreover, it has been reported that VLDLR mRNA levels are increased in the post-mortem brain of autistic patients.METHODS:We generated transgenic (Tg) rats overexpressing Vldlr, and examined their histological and behavioral features.RESULTS:Spontaneous locomotor activity was significantly increased in Tg rats, without detectable changes in brain histology. Additionally, Tg rats tended to show performance deficits in the radial maze task, suggesting that their spatial working memory was slightly impaired. Thus, Vldlr levels may be involved in determining locomotor activity and memory function.CONCLUSIONS:Unlike reeler mice, patients with neurodevelopmental or psychiatric disorders do not show striking neuroanatomical aberrations. Therefore, it is notable, from a clinical point of view, that we observed behavioral phenotypes in Vldlr-Tg rats in the absence of neuroanatomical abnormalities. En ligne : http://dx.doi.org/10.1186/2040-2392-3-11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Vldlr overexpression causes hyperactivity in rats [Texte imprimé et/ou numérique] / Keiko IWATA, Auteur ; Nobuo IZUMO, Auteur ; Hideo MATSUZAKI, Auteur ; Takayuki MANABE, Auteur ; Yukiko ISHIBASHI, Auteur ; Yukio ICHITANI, Auteur ; Kazuo YAMADA, Auteur ; Ismail THANSEEM, Auteur ; Ayyappan ANITHA, Auteur ; Mahesh VASU, Auteur ; Chie SHIMMURA, Auteur ; Tomoyasu WAKUDA, Auteur ; Yosuke KAMENO, Auteur ; Taro TAKAHASHI, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Kazuhiko NAKAMURA, Auteur ; Norio MORI, Auteur . - 2012 . - 9 p. Langues : Anglais (eng) in Molecular Autism > (October 2012) . - 9 p. Mots-clés : Hyperactivity  Neurodevelopmental disorder  Psychiatric disorder  Reelin  Transgenic rat  Vldlr Index. décimale : PER Périodiques Résumé : BACKGROUND:Reelin regulates neuronal positioning in cortical brain structures and neuronal migration via binding to the lipoprotein receptors Vldlr and Lrp8. Reeler mutant mice display severe brain morphological defects and behavioral abnormalities. Several reports have implicated reelin signaling in the etiology of neurodevelopmental and psychiatric disorders, including autism, schizophrenia, bipolar disorder, and depression. Moreover, it has been reported that VLDLR mRNA levels are increased in the post-mortem brain of autistic patients.METHODS:We generated transgenic (Tg) rats overexpressing Vldlr, and examined their histological and behavioral features.RESULTS:Spontaneous locomotor activity was significantly increased in Tg rats, without detectable changes in brain histology. Additionally, Tg rats tended to show performance deficits in the radial maze task, suggesting that their spatial working memory was slightly impaired. Thus, Vldlr levels may be involved in determining locomotor activity and memory function.CONCLUSIONS:Unlike reeler mice, patients with neurodevelopmental or psychiatric disorders do not show striking neuroanatomical aberrations. Therefore, it is notable, from a clinical point of view, that we observed behavioral phenotypes in Vldlr-Tg rats in the absence of neuroanatomical abnormalities. En ligne : http://dx.doi.org/10.1186/2040-2392-3-11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

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