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

Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism / Chie SHIMMURA in Molecular Autism, (March 2013)  

Public ISBD [article]  inMolecular Autism > (March 2013) . - 7 p. Titre : Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism Type de document : Texte imprimé et/ou numérique Auteurs : Chie SHIMMURA, Auteur ; Katsuaki SUZUKI, Auteur ; Yasuhide IWATA, Auteur ; Kenji J. TSUCHIYA, Auteur ; Koji OHNO, Auteur ; Hideo MATSUZAKI, Auteur ; Keiko IWATA, Auteur ; Yosuke KAMENO, Auteur ; Taro TAKAHASHI, Auteur ; Tomoyasu WAKUDA, Auteur ; Kazuhiko NAKAMURA, Auteur ; Kenji HASHIMOTO, Auteur ; Norio MORI, Auteur Année de publication : 2013 Article en page(s) : 7 p. Langues : Anglais (eng) Mots-clés : Autism  Glutamate  Glutaminase  Glutamate-glutamine cycle  Anterior cingulate cortex Index. décimale : PER Périodiques Résumé : BACKGROUND:Accumulating evidence suggests that dysfunction in the glutamatergic system may underlie the pathophysiology of autism. The anterior cingulate cortex (ACC) has been implicated in autism as well as in glutamatergic neurotransmission. We hypothesized that alterations in the glutamate-glutamine cycle in the ACC might play a role in the pathophysiology of autism.METHODS:We performed Western blot analyses for the protein expression levels of enzymes in the glutamate-glutamine cycle, including glutamine synthetase, kidney-type glutaminase, liver-type glutaminase, and glutamate dehydrogenases 1 and 2, in the ACC of postmortem brain of individuals with autism (n=7) and control subjects (n=13).RESULTS:We found that the protein levels of kidney-type glutaminase, but not those of the other enzymes measured, in the ACC were significantly lower in subjects with autism than in controls.CONCLUSION:The results suggest that reduced expression of kidney-type glutaminase may account for putative alterations in glutamatergic neurotransmission in the ACC in autism. En ligne : http://dx.doi.org/10.1186/2040-2392-4-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism [Texte imprimé et/ou numérique] / Chie SHIMMURA, Auteur ; Katsuaki SUZUKI, Auteur ; Yasuhide IWATA, Auteur ; Kenji J. TSUCHIYA, Auteur ; Koji OHNO, Auteur ; Hideo MATSUZAKI, Auteur ; Keiko IWATA, Auteur ; Yosuke KAMENO, Auteur ; Taro TAKAHASHI, Auteur ; Tomoyasu WAKUDA, Auteur ; Kazuhiko NAKAMURA, Auteur ; Kenji HASHIMOTO, Auteur ; Norio MORI, Auteur . - 2013 . - 7 p. Langues : Anglais (eng) in Molecular Autism > (March 2013) . - 7 p. Mots-clés : Autism  Glutamate  Glutaminase  Glutamate-glutamine cycle  Anterior cingulate cortex Index. décimale : PER Périodiques Résumé : BACKGROUND:Accumulating evidence suggests that dysfunction in the glutamatergic system may underlie the pathophysiology of autism. The anterior cingulate cortex (ACC) has been implicated in autism as well as in glutamatergic neurotransmission. We hypothesized that alterations in the glutamate-glutamine cycle in the ACC might play a role in the pathophysiology of autism.METHODS:We performed Western blot analyses for the protein expression levels of enzymes in the glutamate-glutamine cycle, including glutamine synthetase, kidney-type glutaminase, liver-type glutaminase, and glutamate dehydrogenases 1 and 2, in the ACC of postmortem brain of individuals with autism (n=7) and control subjects (n=13).RESULTS:We found that the protein levels of kidney-type glutaminase, but not those of the other enzymes measured, in the ACC were significantly lower in subjects with autism than in controls.CONCLUSION:The results suggest that reduced expression of kidney-type glutaminase may account for putative alterations in glutamatergic neurotransmission in the ACC in autism. En ligne : http://dx.doi.org/10.1186/2040-2392-4-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Serum levels of soluble platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 are decreased in subjects with autism spectrum disorder / Yosuke KAMENO in Molecular Autism, (June 2013)  

Public ISBD [article]  inMolecular Autism > (June 2013) . - 6 p. Titre : Serum levels of soluble platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 are decreased in subjects with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Yosuke KAMENO, Auteur ; Keiko IWATA, Auteur ; Hideo MATSUZAKI, Auteur ; Taishi MIYACHI, Auteur ; Kenji J. TSUCHIYA, Auteur ; Kaori MATSUMOTO, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Kazuhiko NAKAMURA, Auteur ; Masato MAEKAWA, Auteur ; Masatsugu TSUJII, Auteur ; Toshirou SUGIYAMA, Auteur ; Norio MORI, Auteur Année de publication : 2013 Article en page(s) : 6 p. Langues : Anglais (eng) Mots-clés : Autism  Human serum  Adhesion molecules  Platelet-endothelial adhesion molecule-1  Platelet selectin  Endothelial selectin  Intracellular adhesion molecule-1  Vascular cell adhesion molecule-1 Index. décimale : PER Périodiques Résumé : Background Adhesion molecules, such as platelet-endothelial adhesion molecule-1 (PECAM-1), platelet selectin (P-selectin), endothelial selectin (E-selectin), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), are localized on the membranes of activated platelets and leukocytes and on the vascular endothelium. Recently, we measured serum levels of soluble (s) forms of adhesion molecules in adults,18 to 26 years old, with autism spectrum disorder (ASD) and observed low levels of sPECAM-1 and sP-selectin. A subsequent study showed a similar result in children two to four years old with ASD. However, information about school age (five to seventeen years old) ASD subjects is required to determine whether adhesion molecules are also reduced in individuals with ASD in this age range. Findings Twenty-two subjects with high-functioning ASD and 29 healthy age-matched controls were recruited. ELISA was used for sPECAM-1, and a suspension array system was used for sP-selectin, sE-selectin, sICAM-1 and sVCAM-1 measurements. We found that serum levels of sPECAM-1 (U = 91.0, P<0.0001 by Mann–Whitney U test) and sVCAM-1 (U = 168.0, P = 0.0042) were significantly lower in ASD subjects than in controls. Subsequently, we examined the correlations between serum levels of either sPECAM-1 or sVCAM-1 and clinical variables including Autism Diagnostic Interview - Revised subscores and our previous cytokine profile data from the same ASD subjects. However, we did not find any significant correlations between them. Conclusions The present results, taken together with previous results, suggest that sPECAM-1 may play a role in the generation and development of ASD, beginning in childhood and lasting until adulthood. En ligne : http://dx.doi.org/10.1186/2040-2392-4-19 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 [article] Serum levels of soluble platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 are decreased in subjects with autism spectrum disorder [Texte imprimé et/ou numérique] / Yosuke KAMENO, Auteur ; Keiko IWATA, Auteur ; Hideo MATSUZAKI, Auteur ; Taishi MIYACHI, Auteur ; Kenji J. TSUCHIYA, Auteur ; Kaori MATSUMOTO, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Kazuhiko NAKAMURA, Auteur ; Masato MAEKAWA, Auteur ; Masatsugu TSUJII, Auteur ; Toshirou SUGIYAMA, Auteur ; Norio MORI, Auteur . - 2013 . - 6 p. Langues : Anglais (eng) in Molecular Autism > (June 2013) . - 6 p. Mots-clés : Autism  Human serum  Adhesion molecules  Platelet-endothelial adhesion molecule-1  Platelet selectin  Endothelial selectin  Intracellular adhesion molecule-1  Vascular cell adhesion molecule-1 Index. décimale : PER Périodiques Résumé : Background Adhesion molecules, such as platelet-endothelial adhesion molecule-1 (PECAM-1), platelet selectin (P-selectin), endothelial selectin (E-selectin), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), are localized on the membranes of activated platelets and leukocytes and on the vascular endothelium. Recently, we measured serum levels of soluble (s) forms of adhesion molecules in adults,18 to 26 years old, with autism spectrum disorder (ASD) and observed low levels of sPECAM-1 and sP-selectin. A subsequent study showed a similar result in children two to four years old with ASD. However, information about school age (five to seventeen years old) ASD subjects is required to determine whether adhesion molecules are also reduced in individuals with ASD in this age range. Findings Twenty-two subjects with high-functioning ASD and 29 healthy age-matched controls were recruited. ELISA was used for sPECAM-1, and a suspension array system was used for sP-selectin, sE-selectin, sICAM-1 and sVCAM-1 measurements. We found that serum levels of sPECAM-1 (U = 91.0, P<0.0001 by Mann–Whitney U test) and sVCAM-1 (U = 168.0, P = 0.0042) were significantly lower in ASD subjects than in controls. Subsequently, we examined the correlations between serum levels of either sPECAM-1 or sVCAM-1 and clinical variables including Autism Diagnostic Interview - Revised subscores and our previous cytokine profile data from the same ASD subjects. However, we did not find any significant correlations between them. Conclusions The present results, taken together with previous results, suggest that sPECAM-1 may play a role in the generation and development of ASD, beginning in childhood and lasting until adulthood. En ligne : http://dx.doi.org/10.1186/2040-2392-4-19 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211

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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