Neuroglial Involvement in Abnormal Glutamate Transport in the Cochlear Nuclei of the Igf1-/- Mouse

Insulin-like growth factor 1 (IGF-1) is a powerful regulator of synaptic activity and a deficit in this protein has a profound impact on neurotransmission, mostly on excitatory synapses in both the developing and mature auditory system. Adult Igf1-/- mice are animal models for the study of human syn...

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Autores: Fuentes Santamaría, Verónica, Alvarado Romero, Juan Carlos, Rodríguez de la Rosa, Lourdes, Juiz Gómez, José Manuel, Varela Nieto, Isabel
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/32905
Acceso en línea:https://www.frontiersin.org/articles/10.3389/fncel.2019.00067/full
https://hdl.handle.net/10578/32905
Access Level:acceso abierto
Palabra clave:Astrocytes
Cochlear nucleus
Glutamate receptors
Hearing loss
IGF-1
Microglia
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spelling Neuroglial Involvement in Abnormal Glutamate Transport in the Cochlear Nuclei of the Igf1-/- MouseFuentes Santamaría, VerónicaAlvarado Romero, Juan CarlosRodríguez de la Rosa, LourdesJuiz Gómez, José ManuelVarela Nieto, IsabelAstrocytesCochlear nucleusGlutamate receptorsHearing lossIGF-1MicrogliaInsulin-like growth factor 1 (IGF-1) is a powerful regulator of synaptic activity and a deficit in this protein has a profound impact on neurotransmission, mostly on excitatory synapses in both the developing and mature auditory system. Adult Igf1-/- mice are animal models for the study of human syndromic deafness; they show altered cochlear projection patterns into abnormally developed auditory neurons along with impaired glutamate uptake in the cochlear nuclei, phenomena that probably reflect disruptions in neuronal circuits. To determine the cellular mechanisms that might be involved in regulating excitatory synaptic plasticity in 4-month-old Igf1-/- mice, modifications to neuroglia, astroglial glutamate transporters (GLTs) and metabotropic glutamate receptors (mGluRs) were assessed in the cochlear nuclei. The Igf1-/- mice show significant decreases in IBA1 (an ionized calcium-binding adapter) and glial fibrillary acidic protein (GFAP) mRNA expression and protein accumulation, as well as dampened mGluR expression in conjunction with enhanced glutamate transporter 1 (GLT1) expression. By contrast, no differences were observed in the expression of glutamate aspartate transporter (GLAST) between these Igf1-/- mice and their heterozygous or wildtype littermates. These observations suggest that congenital IGF-1 deficiency may lead to alterations in microglia and astrocytes, an upregulation of GLT1, and the downregulation of groups I, II and III mGluRs. Understanding the molecular, biochemical and morphological mechanisms underlying neuronal plasticity in a mouse model of hearing deficits will give us insight into new therapeutic strategies that could help to maintain or even improve residual hearing when human deafness is related to IGF-1 deficiency.Frontiers Media SA202420242019info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://www.frontiersin.org/articles/10.3389/fncel.2019.00067/fullhttps://hdl.handle.net/10578/32905reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésSAF2016-788898-C2-1RSeventh Framework Programme (FP7)-HEALTH2012-INNOVATON (#304925)CIBERER/FEDER ACCI-ER16P5AC7091MINECO/FEDER (SAF2014-53979-R)FP7-PEOPLE-2013-IAPP TARGEARCIBERER/FEDER (ACCIER16P5AC7091)CIBERER/FEDER (ER17P5AC7612)info:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/329052026-05-27T07:36:41Z
dc.title.none.fl_str_mv Neuroglial Involvement in Abnormal Glutamate Transport in the Cochlear Nuclei of the Igf1-/- Mouse
title Neuroglial Involvement in Abnormal Glutamate Transport in the Cochlear Nuclei of the Igf1-/- Mouse
spellingShingle Neuroglial Involvement in Abnormal Glutamate Transport in the Cochlear Nuclei of the Igf1-/- Mouse
Fuentes Santamaría, Verónica
Astrocytes
Cochlear nucleus
Glutamate receptors
Hearing loss
IGF-1
Microglia
title_short Neuroglial Involvement in Abnormal Glutamate Transport in the Cochlear Nuclei of the Igf1-/- Mouse
title_full Neuroglial Involvement in Abnormal Glutamate Transport in the Cochlear Nuclei of the Igf1-/- Mouse
title_fullStr Neuroglial Involvement in Abnormal Glutamate Transport in the Cochlear Nuclei of the Igf1-/- Mouse
title_full_unstemmed Neuroglial Involvement in Abnormal Glutamate Transport in the Cochlear Nuclei of the Igf1-/- Mouse
title_sort Neuroglial Involvement in Abnormal Glutamate Transport in the Cochlear Nuclei of the Igf1-/- Mouse
dc.creator.none.fl_str_mv Fuentes Santamaría, Verónica
Alvarado Romero, Juan Carlos
Rodríguez de la Rosa, Lourdes
Juiz Gómez, José Manuel
Varela Nieto, Isabel
author Fuentes Santamaría, Verónica
author_facet Fuentes Santamaría, Verónica
Alvarado Romero, Juan Carlos
Rodríguez de la Rosa, Lourdes
Juiz Gómez, José Manuel
Varela Nieto, Isabel
author_role author
author2 Alvarado Romero, Juan Carlos
Rodríguez de la Rosa, Lourdes
Juiz Gómez, José Manuel
Varela Nieto, Isabel
author2_role author
author
author
author
dc.subject.none.fl_str_mv Astrocytes
Cochlear nucleus
Glutamate receptors
Hearing loss
IGF-1
Microglia
topic Astrocytes
Cochlear nucleus
Glutamate receptors
Hearing loss
IGF-1
Microglia
description Insulin-like growth factor 1 (IGF-1) is a powerful regulator of synaptic activity and a deficit in this protein has a profound impact on neurotransmission, mostly on excitatory synapses in both the developing and mature auditory system. Adult Igf1-/- mice are animal models for the study of human syndromic deafness; they show altered cochlear projection patterns into abnormally developed auditory neurons along with impaired glutamate uptake in the cochlear nuclei, phenomena that probably reflect disruptions in neuronal circuits. To determine the cellular mechanisms that might be involved in regulating excitatory synaptic plasticity in 4-month-old Igf1-/- mice, modifications to neuroglia, astroglial glutamate transporters (GLTs) and metabotropic glutamate receptors (mGluRs) were assessed in the cochlear nuclei. The Igf1-/- mice show significant decreases in IBA1 (an ionized calcium-binding adapter) and glial fibrillary acidic protein (GFAP) mRNA expression and protein accumulation, as well as dampened mGluR expression in conjunction with enhanced glutamate transporter 1 (GLT1) expression. By contrast, no differences were observed in the expression of glutamate aspartate transporter (GLAST) between these Igf1-/- mice and their heterozygous or wildtype littermates. These observations suggest that congenital IGF-1 deficiency may lead to alterations in microglia and astrocytes, an upregulation of GLT1, and the downregulation of groups I, II and III mGluRs. Understanding the molecular, biochemical and morphological mechanisms underlying neuronal plasticity in a mouse model of hearing deficits will give us insight into new therapeutic strategies that could help to maintain or even improve residual hearing when human deafness is related to IGF-1 deficiency.
publishDate 2019
dc.date.none.fl_str_mv 2019
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://www.frontiersin.org/articles/10.3389/fncel.2019.00067/full
https://hdl.handle.net/10578/32905
url https://www.frontiersin.org/articles/10.3389/fncel.2019.00067/full
https://hdl.handle.net/10578/32905
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv SAF2016-788898-C2-1R
Seventh Framework Programme (FP7)-HEALTH2012-INNOVATON (#304925)
CIBERER/FEDER ACCI-ER16P5AC7091
MINECO/FEDER (SAF2014-53979-R)
FP7-PEOPLE-2013-IAPP TARGEAR
CIBERER/FEDER (ACCIER16P5AC7091)
CIBERER/FEDER (ER17P5AC7612)
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media SA
publisher.none.fl_str_mv Frontiers Media SA
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Universidad de Castilla-La Mancha
instname_str Universidad de Castilla-La Mancha
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
collection RUIdeRA. Repositorio Institucional de la UCLM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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