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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/21077
Ver los metadatos del registro completo
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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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1844613691776958464 |
score |
13.070432 |