Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampus

Autores
Litvak, Einav Tamara; Traetta, Marianela Evelyn; Codagnone, Martín Gabriel; Malleville Corpa, María José; Uccelli, Nonthué Alejandra; Reines, Analia Gabriela
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Autism spectrum disorders (ASD) are a group of severe neurodevelopmental disabilities of unknown etiology, characterized by social interaction deficits and increased stereotyped behaviors. Although ASD incidence is four times higher in boys than in girls, sex differences have not been clarified. The rat model of autism induced by prenatal exposure to valproic acid (VPA) has been characterized in males (MVPA), while female rat VPA (FVPA) phenotype is still controversial. The aim of this work was to further characterize the behavioral profile of FVPA and explore structural synapse markers, cell adhesion molecules and microglia morphology in the medial prefrontal cortex (mPFC) and the hippocampus. At early postnatal days (PND)7-15, and similar to MVPA, FVPA showed growth and maturation deficits: delayed eye opening, lower body weight, altered negative geotaxis, higher latencies to nest seeking response and a deficit in swimming performance. At PND30-35, like MVPA, FVPA showed a reduced number of interactions in the social play behavior test, but they exhibited distinctive pinning features. Contrary to MVPA that showed an exploratory deficit and increased stereotypical activities, FVPA matched control female rat behavior. Notably, at PND35, mPFC of FVPA and MVPA showed an increase in synaptophysin (SYN) and neural cell adhesion molecule (NCAM) and a similar ramified/unramified microglia (Iba+) ratio. However, the polysialylated form of NCAM (PSA-NCAM) was increased in FVPA but decreased in MVPA. In the hippocampus, both FVPA and MVPA showed reduced SYN labeling and increased NCAM but only FVPA displayed a higher proportion of unramified microglia. Also, PSA-NCAM levels were preserved in FVPA but reduced in MVPA. To sum up, FVPA exhibit a mild behavioral phenotype accompanied with a distinctive microglia profile and NCAM/PSA-NCAM ratio that may facilitate structural synapse remodeling and plasticity.
Fil: Litvak, Einav Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Traetta, Marianela Evelyn. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Codagnone, Martín Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Malleville Corpa, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Uccelli, Nonthué Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Reines, Analia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología.
Virtual
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
Materia
AUTISM
SOCIAL BEHAVIOR
ADHESION MOLECULES
SEXUAL DIFFERENCES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/198921
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/198921
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampusLitvak, Einav TamaraTraetta, Marianela EvelynCodagnone, Martín GabrielMalleville Corpa, María JoséUccelli, Nonthué AlejandraReines, Analia GabrielaAUTISMSOCIAL BEHAVIORADHESION MOLECULESSEXUAL DIFFERENCEShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Autism spectrum disorders (ASD) are a group of severe neurodevelopmental disabilities of unknown etiology, characterized by social interaction deficits and increased stereotyped behaviors. Although ASD incidence is four times higher in boys than in girls, sex differences have not been clarified. The rat model of autism induced by prenatal exposure to valproic acid (VPA) has been characterized in males (MVPA), while female rat VPA (FVPA) phenotype is still controversial. The aim of this work was to further characterize the behavioral profile of FVPA and explore structural synapse markers, cell adhesion molecules and microglia morphology in the medial prefrontal cortex (mPFC) and the hippocampus. At early postnatal days (PND)7-15, and similar to MVPA, FVPA showed growth and maturation deficits: delayed eye opening, lower body weight, altered negative geotaxis, higher latencies to nest seeking response and a deficit in swimming performance. At PND30-35, like MVPA, FVPA showed a reduced number of interactions in the social play behavior test, but they exhibited distinctive pinning features. Contrary to MVPA that showed an exploratory deficit and increased stereotypical activities, FVPA matched control female rat behavior. Notably, at PND35, mPFC of FVPA and MVPA showed an increase in synaptophysin (SYN) and neural cell adhesion molecule (NCAM) and a similar ramified/unramified microglia (Iba+) ratio. However, the polysialylated form of NCAM (PSA-NCAM) was increased in FVPA but decreased in MVPA. In the hippocampus, both FVPA and MVPA showed reduced SYN labeling and increased NCAM but only FVPA displayed a higher proportion of unramified microglia. Also, PSA-NCAM levels were preserved in FVPA but reduced in MVPA. To sum up, FVPA exhibit a mild behavioral phenotype accompanied with a distinctive microglia profile and NCAM/PSA-NCAM ratio that may facilitate structural synapse remodeling and plasticity.Fil: Litvak, Einav Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Traetta, Marianela Evelyn. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Codagnone, Martín Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Malleville Corpa, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Uccelli, Nonthué Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Reines, Analia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaLXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología.VirtualArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina de FisiologíaFundación Revista Medicina2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/198921Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampus; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología.; Virtual; Argentina; 2020; 109-109CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/reunion-anualNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T09:37:59Zoai:ri.conicet.gov.ar:11336/198921instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-11-12 09:37:59.65CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampus
title Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampus
spellingShingle Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampus
Litvak, Einav Tamara
AUTISM
SOCIAL BEHAVIOR
ADHESION MOLECULES
SEXUAL DIFFERENCES
title_short Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampus
title_full Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampus
title_fullStr Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampus
title_full_unstemmed Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampus
title_sort Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampus
dc.creator.none.fl_str_mv Litvak, Einav Tamara
Traetta, Marianela Evelyn
Codagnone, Martín Gabriel
Malleville Corpa, María José
Uccelli, Nonthué Alejandra
Reines, Analia Gabriela
author Litvak, Einav Tamara
author_facet Litvak, Einav Tamara
Traetta, Marianela Evelyn
Codagnone, Martín Gabriel
Malleville Corpa, María José
Uccelli, Nonthué Alejandra
Reines, Analia Gabriela
author_role author
author2 Traetta, Marianela Evelyn
Codagnone, Martín Gabriel
Malleville Corpa, María José
Uccelli, Nonthué Alejandra
Reines, Analia Gabriela
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv AUTISM
SOCIAL BEHAVIOR
ADHESION MOLECULES
SEXUAL DIFFERENCES
topic AUTISM
SOCIAL BEHAVIOR
ADHESION MOLECULES
SEXUAL DIFFERENCES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Autism spectrum disorders (ASD) are a group of severe neurodevelopmental disabilities of unknown etiology, characterized by social interaction deficits and increased stereotyped behaviors. Although ASD incidence is four times higher in boys than in girls, sex differences have not been clarified. The rat model of autism induced by prenatal exposure to valproic acid (VPA) has been characterized in males (MVPA), while female rat VPA (FVPA) phenotype is still controversial. The aim of this work was to further characterize the behavioral profile of FVPA and explore structural synapse markers, cell adhesion molecules and microglia morphology in the medial prefrontal cortex (mPFC) and the hippocampus. At early postnatal days (PND)7-15, and similar to MVPA, FVPA showed growth and maturation deficits: delayed eye opening, lower body weight, altered negative geotaxis, higher latencies to nest seeking response and a deficit in swimming performance. At PND30-35, like MVPA, FVPA showed a reduced number of interactions in the social play behavior test, but they exhibited distinctive pinning features. Contrary to MVPA that showed an exploratory deficit and increased stereotypical activities, FVPA matched control female rat behavior. Notably, at PND35, mPFC of FVPA and MVPA showed an increase in synaptophysin (SYN) and neural cell adhesion molecule (NCAM) and a similar ramified/unramified microglia (Iba+) ratio. However, the polysialylated form of NCAM (PSA-NCAM) was increased in FVPA but decreased in MVPA. In the hippocampus, both FVPA and MVPA showed reduced SYN labeling and increased NCAM but only FVPA displayed a higher proportion of unramified microglia. Also, PSA-NCAM levels were preserved in FVPA but reduced in MVPA. To sum up, FVPA exhibit a mild behavioral phenotype accompanied with a distinctive microglia profile and NCAM/PSA-NCAM ratio that may facilitate structural synapse remodeling and plasticity.
Fil: Litvak, Einav Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Traetta, Marianela Evelyn. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Codagnone, Martín Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Malleville Corpa, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Uccelli, Nonthué Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Reines, Analia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología.
Virtual
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
description Autism spectrum disorders (ASD) are a group of severe neurodevelopmental disabilities of unknown etiology, characterized by social interaction deficits and increased stereotyped behaviors. Although ASD incidence is four times higher in boys than in girls, sex differences have not been clarified. The rat model of autism induced by prenatal exposure to valproic acid (VPA) has been characterized in males (MVPA), while female rat VPA (FVPA) phenotype is still controversial. The aim of this work was to further characterize the behavioral profile of FVPA and explore structural synapse markers, cell adhesion molecules and microglia morphology in the medial prefrontal cortex (mPFC) and the hippocampus. At early postnatal days (PND)7-15, and similar to MVPA, FVPA showed growth and maturation deficits: delayed eye opening, lower body weight, altered negative geotaxis, higher latencies to nest seeking response and a deficit in swimming performance. At PND30-35, like MVPA, FVPA showed a reduced number of interactions in the social play behavior test, but they exhibited distinctive pinning features. Contrary to MVPA that showed an exploratory deficit and increased stereotypical activities, FVPA matched control female rat behavior. Notably, at PND35, mPFC of FVPA and MVPA showed an increase in synaptophysin (SYN) and neural cell adhesion molecule (NCAM) and a similar ramified/unramified microglia (Iba+) ratio. However, the polysialylated form of NCAM (PSA-NCAM) was increased in FVPA but decreased in MVPA. In the hippocampus, both FVPA and MVPA showed reduced SYN labeling and increased NCAM but only FVPA displayed a higher proportion of unramified microglia. Also, PSA-NCAM levels were preserved in FVPA but reduced in MVPA. To sum up, FVPA exhibit a mild behavioral phenotype accompanied with a distinctive microglia profile and NCAM/PSA-NCAM ratio that may facilitate structural synapse remodeling and plasticity.
publishDate 2020
dc.date.none.fl_str_mv 2020
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info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/198921
Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampus; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología.; Virtual; Argentina; 2020; 109-109
CONICET Digital
CONICET
url http://hdl.handle.net/11336/198921
identifier_str_mv Mild VPA behavioral phenotype in female rats: Evidence of structural synapse remodeling in the medial prefrontal cortex and the hippocampus; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología.; Virtual; Argentina; 2020; 109-109
CONICET Digital
CONICET
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