Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons

Autores
Beck, Paige; Mahaffey, Susan; Urbano Suarez, Francisco Jose; Garcia Rill, Edgar
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The pedunculopontine nucleus (PPN), the cholinergic arm of the reticular activating system, regulates waking and rapid eye movement sleep. Here, we demonstrate immunohistochemical labeling of the leptin receptor signaling isoform in PPN neurons, and investigated the effects of G-protein modulation and the leptin triple antagonist (TA) on the action of leptin in the PPN. Whole-cell patch clamp recordings were performed in rat brainstem slices from 9 to 17 day old pups. Previous results showed that leptin caused a partial blockade of sodium (INa) and h-current (IH) in PPN neurons. TA (100 nM) reduced the blockade of INa (~ 50% reduction) and IH (~ 93% reduction) caused by leptin. Intracellular guanosine 5′-[b-thio] diphosphate trilithium salt (a G-protein inhibitor) significantly reduced the effect of leptin on INa(~ 60% reduction) but not on IH (~ 25% reduction). Intracellular GTPcS (a G-protein activator) reduced the effect of leptin on both INa (~ 80% reduction) and IH (~ 90% reduction). These results suggest that the effects of leptin on the intrinsic properties of PPN neurons are leptin receptor- and G-protein dependent. We also found that leptin enhanced NMDA receptor-mediated responses in single neurons and in the PPN population as a whole, an effect blocked by TA. These experiments further strengthen the association between leptin dysregulation and sleep disturbances.
Fil: Beck, Paige. University Of Arkansas For Medical Sciences; Estados Unidos
Fil: Mahaffey, Susan. University Of Arkansas For Medical Sciences; Estados Unidos
Fil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Garcia Rill, Edgar. University Of Arkansas For Medical Sciences; Estados Unidos
Materia
Pedundulopontine Nucleus
Brainstem
Leptin
Sodium Channels
H-Current
G-Protein
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:11336/21077

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spelling Role of G-proteins in the effects of leptin on pedunculopontine nucleus neuronsBeck, PaigeMahaffey, SusanUrbano Suarez, Francisco JoseGarcia Rill, EdgarPedundulopontine NucleusBrainstemLeptinSodium ChannelsH-CurrentG-Proteinhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The pedunculopontine nucleus (PPN), the cholinergic arm of the reticular activating system, regulates waking and rapid eye movement sleep. Here, we demonstrate immunohistochemical labeling of the leptin receptor signaling isoform in PPN neurons, and investigated the effects of G-protein modulation and the leptin triple antagonist (TA) on the action of leptin in the PPN. Whole-cell patch clamp recordings were performed in rat brainstem slices from 9 to 17 day old pups. Previous results showed that leptin caused a partial blockade of sodium (INa) and h-current (IH) in PPN neurons. TA (100 nM) reduced the blockade of INa (~ 50% reduction) and IH (~ 93% reduction) caused by leptin. Intracellular guanosine 5′-[b-thio] diphosphate trilithium salt (a G-protein inhibitor) significantly reduced the effect of leptin on INa(~ 60% reduction) but not on IH (~ 25% reduction). Intracellular GTPcS (a G-protein activator) reduced the effect of leptin on both INa (~ 80% reduction) and IH (~ 90% reduction). These results suggest that the effects of leptin on the intrinsic properties of PPN neurons are leptin receptor- and G-protein dependent. We also found that leptin enhanced NMDA receptor-mediated responses in single neurons and in the PPN population as a whole, an effect blocked by TA. These experiments further strengthen the association between leptin dysregulation and sleep disturbances.Fil: Beck, Paige. University Of Arkansas For Medical Sciences; Estados UnidosFil: Mahaffey, Susan. University Of Arkansas For Medical Sciences; Estados UnidosFil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Garcia Rill, Edgar. University Of Arkansas For Medical Sciences; Estados UnidosWiley2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/21077Beck, Paige; Mahaffey, Susan; Urbano Suarez, Francisco Jose; Garcia Rill, Edgar; Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons; Wiley; Journal of Neurochemistry; 126; 6; 6-2013; 705-7140022-3042CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/jnc.12312info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/jnc.12312/abstractinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766503/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:56:16Zoai:ri.conicet.gov.ar:11336/21077instacron: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:34982025-09-29 09:56:16.93CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons
title Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons
spellingShingle Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons
Beck, Paige
Pedundulopontine Nucleus
Brainstem
Leptin
Sodium Channels
H-Current
G-Protein
title_short Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons
title_full Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons
title_fullStr Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons
title_full_unstemmed Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons
title_sort Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons
dc.creator.none.fl_str_mv Beck, Paige
Mahaffey, Susan
Urbano Suarez, Francisco Jose
Garcia Rill, Edgar
author Beck, Paige
author_facet Beck, Paige
Mahaffey, Susan
Urbano Suarez, Francisco Jose
Garcia Rill, Edgar
author_role author
author2 Mahaffey, Susan
Urbano Suarez, Francisco Jose
Garcia Rill, Edgar
author2_role author
author
author
dc.subject.none.fl_str_mv Pedundulopontine Nucleus
Brainstem
Leptin
Sodium Channels
H-Current
G-Protein
topic Pedundulopontine Nucleus
Brainstem
Leptin
Sodium Channels
H-Current
G-Protein
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The pedunculopontine nucleus (PPN), the cholinergic arm of the reticular activating system, regulates waking and rapid eye movement sleep. Here, we demonstrate immunohistochemical labeling of the leptin receptor signaling isoform in PPN neurons, and investigated the effects of G-protein modulation and the leptin triple antagonist (TA) on the action of leptin in the PPN. Whole-cell patch clamp recordings were performed in rat brainstem slices from 9 to 17 day old pups. Previous results showed that leptin caused a partial blockade of sodium (INa) and h-current (IH) in PPN neurons. TA (100 nM) reduced the blockade of INa (~ 50% reduction) and IH (~ 93% reduction) caused by leptin. Intracellular guanosine 5′-[b-thio] diphosphate trilithium salt (a G-protein inhibitor) significantly reduced the effect of leptin on INa(~ 60% reduction) but not on IH (~ 25% reduction). Intracellular GTPcS (a G-protein activator) reduced the effect of leptin on both INa (~ 80% reduction) and IH (~ 90% reduction). These results suggest that the effects of leptin on the intrinsic properties of PPN neurons are leptin receptor- and G-protein dependent. We also found that leptin enhanced NMDA receptor-mediated responses in single neurons and in the PPN population as a whole, an effect blocked by TA. These experiments further strengthen the association between leptin dysregulation and sleep disturbances.
Fil: Beck, Paige. University Of Arkansas For Medical Sciences; Estados Unidos
Fil: Mahaffey, Susan. University Of Arkansas For Medical Sciences; Estados Unidos
Fil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Garcia Rill, Edgar. University Of Arkansas For Medical Sciences; Estados Unidos
description The pedunculopontine nucleus (PPN), the cholinergic arm of the reticular activating system, regulates waking and rapid eye movement sleep. Here, we demonstrate immunohistochemical labeling of the leptin receptor signaling isoform in PPN neurons, and investigated the effects of G-protein modulation and the leptin triple antagonist (TA) on the action of leptin in the PPN. Whole-cell patch clamp recordings were performed in rat brainstem slices from 9 to 17 day old pups. Previous results showed that leptin caused a partial blockade of sodium (INa) and h-current (IH) in PPN neurons. TA (100 nM) reduced the blockade of INa (~ 50% reduction) and IH (~ 93% reduction) caused by leptin. Intracellular guanosine 5′-[b-thio] diphosphate trilithium salt (a G-protein inhibitor) significantly reduced the effect of leptin on INa(~ 60% reduction) but not on IH (~ 25% reduction). Intracellular GTPcS (a G-protein activator) reduced the effect of leptin on both INa (~ 80% reduction) and IH (~ 90% reduction). These results suggest that the effects of leptin on the intrinsic properties of PPN neurons are leptin receptor- and G-protein dependent. We also found that leptin enhanced NMDA receptor-mediated responses in single neurons and in the PPN population as a whole, an effect blocked by TA. These experiments further strengthen the association between leptin dysregulation and sleep disturbances.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/21077
Beck, Paige; Mahaffey, Susan; Urbano Suarez, Francisco Jose; Garcia Rill, Edgar; Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons; Wiley; Journal of Neurochemistry; 126; 6; 6-2013; 705-714
0022-3042
CONICET Digital
CONICET
url http://hdl.handle.net/11336/21077
identifier_str_mv Beck, Paige; Mahaffey, Susan; Urbano Suarez, Francisco Jose; Garcia Rill, Edgar; Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons; Wiley; Journal of Neurochemistry; 126; 6; 6-2013; 705-714
0022-3042
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/jnc.12312
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/jnc.12312/abstract
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766503/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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