Adult reversal of cognitive phenotypes in neurodevelopmental disorders / Alcino J. SILVA in Journal of Neurodevelopmental Disorders, 1-2 (June 2009)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 1-2 (June 2009) . - p.150-7 Titre : Adult reversal of cognitive phenotypes in neurodevelopmental disorders Type de document : texte imprimé Auteurs : Alcino J. SILVA, Auteur ; Dan EHNINGER, Auteur Article en page(s) : p.150-7 Langues : Anglais (eng) Mots-clés : Animal models  Autism  Neurodevelopmental disorders  Rescue  Treatment Index. décimale : PER Périodiques Résumé : Recent findings in mice suggest that it is possible to reverse certain neurodevelopmental disorders in adults. Changes in development, previously thought to be irreparable in adults, were believed to underlie the neurological and psychiatric phenotypes of a range of common mental health problems with a clear developmental component. As a consequence, most researchers have focused their efforts on understanding the molecular and cellular processes that alter development with the hope that early intervention could prevent the emergent pathology. Unexpectedly, several different animal model studies published recently, including animal models of autism, suggest that it may be possible to reverse neurodevelopmental disorders in adults: Addressing the underlying molecular and cellular deficits in adults could in several cases dramatically improve the neurocognitive phenotypes in these animal models. The findings reviewed here provide hope to millions of individuals afflicted with a wide range of neurodevelopmental disorders, including autism, since they suggest that it may be possible to treat or even cure them in adults. En ligne : http://dx.doi.org/10.1007/s11689-009-9018-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=341 [article] Adult reversal of cognitive phenotypes in neurodevelopmental disorders [texte imprimé] / Alcino J. SILVA, Auteur ; Dan EHNINGER, Auteur . - p.150-7. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 1-2 (June 2009) . - p.150-7 Mots-clés : Animal models  Autism  Neurodevelopmental disorders  Rescue  Treatment Index. décimale : PER Périodiques Résumé : Recent findings in mice suggest that it is possible to reverse certain neurodevelopmental disorders in adults. Changes in development, previously thought to be irreparable in adults, were believed to underlie the neurological and psychiatric phenotypes of a range of common mental health problems with a clear developmental component. As a consequence, most researchers have focused their efforts on understanding the molecular and cellular processes that alter development with the hope that early intervention could prevent the emergent pathology. Unexpectedly, several different animal model studies published recently, including animal models of autism, suggest that it may be possible to reverse neurodevelopmental disorders in adults: Addressing the underlying molecular and cellular deficits in adults could in several cases dramatically improve the neurocognitive phenotypes in these animal models. The findings reviewed here provide hope to millions of individuals afflicted with a wide range of neurodevelopmental disorders, including autism, since they suggest that it may be possible to treat or even cure them in adults. En ligne : http://dx.doi.org/10.1007/s11689-009-9018-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=341

Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA) / Stavros STIVAROS in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 12 p. Titre : Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA) Type de document : texte imprimé Auteurs : Stavros STIVAROS, Auteur ; Shruti GARG, Auteur ; Maria TZIRAKI, Auteur ; Ying CAI, Auteur ; Owen THOMAS, Auteur ; Joseph MELLOR, Auteur ; Andrew A. MORRIS, Auteur ; Carly JIM, Auteur ; Karolina SZUMANSKA-RYT, Auteur ; Laura M. PARKES, Auteur ; Hamied A. HAROON, Auteur ; Daniela MONTALDI, Auteur ; Nicholas WEBB, Auteur ; John KEANE, Auteur ; Francisco Xavier CASTELLANOS, Auteur ; Alcino J. SILVA, Auteur ; Sue HUSON, Auteur ; Simon WILLIAMS, Auteur ; D. GARETH EVANS, Auteur ; Richard EMSLEY, Auteur ; Jonathan GREEN, Auteur Article en page(s) : 12 p. Langues : Anglais (eng) Mots-clés : Autism  Neurofibromatosis type 1  Neuroimaging  Randomised controlled trial  Simvastatin  Statin Index. décimale : PER Périodiques Résumé : Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results: Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (t(12) = - 2.12, p = .055), GABA/Glx ratio (t(12) = - 2.78, p = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p < 0.01). Machine-learning classification of imaging outcomes achieved 79% (p < .05) accuracy differentiating groups at endpoint against chance level (64%, p = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met 'clinical responder' criteria for behavioural outcome. Conclusions: We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network. Trial registration: EU Clinical Trial Register (EudraCT) 2012-005742-38 (www.clinicaltrialsregister.eu). En ligne : http://dx.doi.org/10.1186/s13229-018-0190-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354 [article] Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA) [texte imprimé] / Stavros STIVAROS, Auteur ; Shruti GARG, Auteur ; Maria TZIRAKI, Auteur ; Ying CAI, Auteur ; Owen THOMAS, Auteur ; Joseph MELLOR, Auteur ; Andrew A. MORRIS, Auteur ; Carly JIM, Auteur ; Karolina SZUMANSKA-RYT, Auteur ; Laura M. PARKES, Auteur ; Hamied A. HAROON, Auteur ; Daniela MONTALDI, Auteur ; Nicholas WEBB, Auteur ; John KEANE, Auteur ; Francisco Xavier CASTELLANOS, Auteur ; Alcino J. SILVA, Auteur ; Sue HUSON, Auteur ; Simon WILLIAMS, Auteur ; D. GARETH EVANS, Auteur ; Richard EMSLEY, Auteur ; Jonathan GREEN, Auteur . - 12 p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 12 p. Mots-clés : Autism  Neurofibromatosis type 1  Neuroimaging  Randomised controlled trial  Simvastatin  Statin Index. décimale : PER Périodiques Résumé : Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results: Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (t(12) = - 2.12, p = .055), GABA/Glx ratio (t(12) = - 2.78, p = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p < 0.01). Machine-learning classification of imaging outcomes achieved 79% (p < .05) accuracy differentiating groups at endpoint against chance level (64%, p = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met 'clinical responder' criteria for behavioural outcome. Conclusions: We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network. Trial registration: EU Clinical Trial Register (EudraCT) 2012-005742-38 (www.clinicaltrialsregister.eu). En ligne : http://dx.doi.org/10.1186/s13229-018-0190-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354

Testing the excitation/inhibition imbalance hypothesis in a mouse model of the autism spectrum disorder: in vivo neurospectroscopy and molecular evidence for regional phenotypes / J. GONCALVES in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 47p. Titre : Testing the excitation/inhibition imbalance hypothesis in a mouse model of the autism spectrum disorder: in vivo neurospectroscopy and molecular evidence for regional phenotypes Type de document : texte imprimé Auteurs : J. GONCALVES, Auteur ; Inês R. VIOLANTE, Auteur ; José SERENO, Auteur ; R.A. LEITAO, Auteur ; Ying CAI, Auteur ; Antero ABRUNHOSA, Auteur ; Ana Paula SILVA, Auteur ; Alcino J. SILVA, Auteur ; Miguel CASTELO-BRANCO, Auteur Article en page(s) : 47p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorders  Excitation/inhibition imbalance  GABA(A) receptor  Magnetic resonance spectroscopy  Neurofibromatosis type 1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Excitation/inhibition (E/I) imbalance remains a widely discussed hypothesis in autism spectrum disorders (ASD). The presence of such an imbalance may potentially define a therapeutic target for the treatment of cognitive disabilities related to this pathology. Consequently, the study of monogenic disorders related to autism, such as neurofibromatosis type 1 (NF1), represents a promising approach to isolate mechanisms underlying ASD-related cognitive disabilities. However, the NF1 mouse model showed increased gamma-aminobutyric acid (GABA) neurotransmission, whereas the human disease showed reduced cortical GABA levels. It is therefore important to clarify whether the E/I imbalance hypothesis holds true. We hypothesize that E/I may depend on distinct pre- and postsynaptic push-pull mechanisms that might be are region-dependent. METHODS: In current study, we assessed two critical components of E/I regulation: the concentration of neurotransmitters and levels of GABA(A) receptors. Measurements were performed across the hippocampi, striatum, and prefrontal cortices by combined in vivo magnetic resonance spectroscopy (MRS) and molecular approaches in this ASD-related animal model, the Nf1(+/-) mouse. RESULTS: Cortical and striatal GABA/glutamate ratios were increased. At the postsynaptic level, very high receptor GABA(A) receptor expression was found in hippocampus, disproportionately to the small reduction in GABA levels. Gabaergic tone (either by receptor levels change or GABA/glutamate ratios) seemed therefore to be enhanced in all regions, although by a different mechanism. CONCLUSIONS: Our data provides support for the hypothesis of E/I imbalance in NF1 while showing that pre- and postsynaptic changes are region-specific. All these findings are consistent with our previous physiological evidence of increased inhibitory tone. Such heterogeneity suggests that therapeutic approaches to address neurochemical imbalance in ASD may need to focus on targets where convergent physiological mechanisms can be found. En ligne : http://dx.doi.org/10.1186/s13229-017-0166-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Testing the excitation/inhibition imbalance hypothesis in a mouse model of the autism spectrum disorder: in vivo neurospectroscopy and molecular evidence for regional phenotypes [texte imprimé] / J. GONCALVES, Auteur ; Inês R. VIOLANTE, Auteur ; José SERENO, Auteur ; R.A. LEITAO, Auteur ; Ying CAI, Auteur ; Antero ABRUNHOSA, Auteur ; Ana Paula SILVA, Auteur ; Alcino J. SILVA, Auteur ; Miguel CASTELO-BRANCO, Auteur . - 47p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 47p. Mots-clés : Autism spectrum disorders  Excitation/inhibition imbalance  GABA(A) receptor  Magnetic resonance spectroscopy  Neurofibromatosis type 1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Excitation/inhibition (E/I) imbalance remains a widely discussed hypothesis in autism spectrum disorders (ASD). The presence of such an imbalance may potentially define a therapeutic target for the treatment of cognitive disabilities related to this pathology. Consequently, the study of monogenic disorders related to autism, such as neurofibromatosis type 1 (NF1), represents a promising approach to isolate mechanisms underlying ASD-related cognitive disabilities. However, the NF1 mouse model showed increased gamma-aminobutyric acid (GABA) neurotransmission, whereas the human disease showed reduced cortical GABA levels. It is therefore important to clarify whether the E/I imbalance hypothesis holds true. We hypothesize that E/I may depend on distinct pre- and postsynaptic push-pull mechanisms that might be are region-dependent. METHODS: In current study, we assessed two critical components of E/I regulation: the concentration of neurotransmitters and levels of GABA(A) receptors. Measurements were performed across the hippocampi, striatum, and prefrontal cortices by combined in vivo magnetic resonance spectroscopy (MRS) and molecular approaches in this ASD-related animal model, the Nf1(+/-) mouse. RESULTS: Cortical and striatal GABA/glutamate ratios were increased. At the postsynaptic level, very high receptor GABA(A) receptor expression was found in hippocampus, disproportionately to the small reduction in GABA levels. Gabaergic tone (either by receptor levels change or GABA/glutamate ratios) seemed therefore to be enhanced in all regions, although by a different mechanism. CONCLUSIONS: Our data provides support for the hypothesis of E/I imbalance in NF1 while showing that pre- and postsynaptic changes are region-specific. All these findings are consistent with our previous physiological evidence of increased inhibitory tone. Such heterogeneity suggests that therapeutic approaches to address neurochemical imbalance in ASD may need to focus on targets where convergent physiological mechanisms can be found. En ligne : http://dx.doi.org/10.1186/s13229-017-0166-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

Tuberous Sclerosis and Autism / Dan EHNINGER

Public ISBD in The Autisms / Craig M. POWELL Titre : Tuberous Sclerosis and Autism Type de document : texte imprimé Auteurs : Dan EHNINGER, Auteur ; Alcino J. SILVA, Auteur Année de publication : 2013 Importance : p.147-160 Langues : Anglais (eng) Index. décimale : SCI-D SCI-D - Neurosciences Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=189 in The Autisms / Craig M. POWELL Tuberous Sclerosis and Autism [texte imprimé] / Dan EHNINGER, Auteur ; Alcino J. SILVA, Auteur . - 2013 . - p.147-160. Langues : Anglais (eng) Index. décimale : SCI-D SCI-D - Neurosciences Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=189

Exemplaires(0)

Disponibilité
aucun exemplaire

---

1 (1 - 4 / 4) Par page : 25 50 100 200