Mutation of Semaphorin-6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology.

Hdl Handle:
http://hdl.handle.net/10147/238792
Title:
Mutation of Semaphorin-6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology.
Authors:
Rünker, Annette E; O'Tuathaigh, Colm; Dunleavy, Mark; Morris, Derek W; Little, Graham E; Corvin, Aiden P; Gill, Michael; Henshall, David C; Waddington, John L; Mitchell, Kevin J
Affiliation:
Smurfit Institute of Genetics and Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Citation:
Mutation of Semaphorin-6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology. 2011, 6 (11):e26488 PLoS ONE
Journal:
PloS one
Issue Date:
2011
URI:
http://hdl.handle.net/10147/238792
DOI:
10.1371/journal.pone.0026488
PubMed ID:
22132072
Abstract:
Psychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism.
Item Type:
Article
Language:
en
MeSH:
Animals; Anxiety; Behavior, Animal; Disease Models, Animal; Female; Gait; Humans; Limbic System; Locomotion; Male; Memory; Mental Disorders; Mice; Mice, Inbred C57BL; Mice, Neurologic Mutants; Mutation; Nerve Net; Phenotype; Prefrontal Cortex; Semaphorins
ISSN:
1932-6203

Full metadata record

DC FieldValue Language
dc.contributor.authorRünker, Annette Een_GB
dc.contributor.authorO'Tuathaigh, Colmen_GB
dc.contributor.authorDunleavy, Marken_GB
dc.contributor.authorMorris, Derek Wen_GB
dc.contributor.authorLittle, Graham Een_GB
dc.contributor.authorCorvin, Aiden Pen_GB
dc.contributor.authorGill, Michaelen_GB
dc.contributor.authorHenshall, David Cen_GB
dc.contributor.authorWaddington, John Len_GB
dc.contributor.authorMitchell, Kevin Jen_GB
dc.date.accessioned2012-08-15T14:08:04Z-
dc.date.available2012-08-15T14:08:04Z-
dc.date.issued2011-
dc.identifier.citationMutation of Semaphorin-6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology. 2011, 6 (11):e26488 PLoS ONEen_GB
dc.identifier.issn1932-6203-
dc.identifier.pmid22132072-
dc.identifier.doi10.1371/journal.pone.0026488-
dc.identifier.urihttp://hdl.handle.net/10147/238792-
dc.description.abstractPsychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to PloS oneen_GB
dc.subject.meshAnimals-
dc.subject.meshAnxiety-
dc.subject.meshBehavior, Animal-
dc.subject.meshDisease Models, Animal-
dc.subject.meshFemale-
dc.subject.meshGait-
dc.subject.meshHumans-
dc.subject.meshLimbic System-
dc.subject.meshLocomotion-
dc.subject.meshMale-
dc.subject.meshMemory-
dc.subject.meshMental Disorders-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshMice, Neurologic Mutants-
dc.subject.meshMutation-
dc.subject.meshNerve Net-
dc.subject.meshPhenotype-
dc.subject.meshPrefrontal Cortex-
dc.subject.meshSemaphorins-
dc.titleMutation of Semaphorin-6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology.en_GB
dc.typeArticleen
dc.contributor.departmentSmurfit Institute of Genetics and Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.en_GB
dc.identifier.journalPloS oneen_GB
dc.description.provinceLeinsteren

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