Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursors

Autores
Wenker, Shirley Denise; Gradaschi, Victoria; Farias, Maria Isabel; Ferrari, Carina Cynthia; Zeng, Xianming; Pitossi, Fernando Juan
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Parkinson’s disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons (DAn) of the nigrostriatal system. Studies in animal models of PD have provided proof of concept that transplantation of DA precursors can relieve parkinsonian symptoms. However, a major limiting factor of this strategy is the poor survival rate of grafted DAn. This could be due to host inflammatory response, among other factors. Our previous results demonstrated a host primary response related to the graft of human dopaminergic precursors (DA14), with an increase of host-MHCII positive cells. Expression of tumor necrosis factor-alpha (TNF-alpha) was also detected on hostED1 positive cells. We aim to study the impact of the proinflammatory environment on DA14 cells and the effect of a TNFalpha inhibitor on an in vitro approach. DA14 cells were exposed to conditioned media (CM) from basal or activated BV2 microglial cells during 4 days. A significant increase in cell death was observed by fluorescence microscopy after Hoechst staining in DA14 cultures exposed with CM from activated microglia (p<0.05). This result was in accordance to a decrease in the number of Tyrosine hydroxylase (TH) positive cells detected by immunofluorescence (p<0.01). Neurite length measurement was performed to evaluate the differentiation process. A decrease in neurite length of TH positive cells was detected in DA14 cultures incubated with CM from activated microglia (p<0.05). In order to study the relevance of TNFalpha, DA14 cells were co-incubated with CM from basal or activated BV2 cells and the TNF-alpha inhibitor, Etanercept. Inhibition of TNF-alpha was able to avoid morphological alterations (p<0.05) and diminution of DA cells (p<0.05). Our results suggest that the pro-inflammatory microenvironment has a negative impact on survival and differentiation of DA14 cells. TNF-alpha inhibition could be an interesting strategy in order to improve survival of DA precursors.
Fil: Wenker, Shirley Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Gradaschi, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Farias, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Ferrari, Carina Cynthia. Hospital Italiano; Argentina
Fil: Zeng, Xianming. Buck Institute For Research On Aging; Estados Unidos
Fil: Pitossi, Fernando Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Materia
PARKINSON
INFLAMMATION
DOPAMINERGIC-PRECURSORS
CELL-SURVIVAL
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:11336/174556
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursorsWenker, Shirley DeniseGradaschi, VictoriaFarias, Maria IsabelFerrari, Carina CynthiaZeng, XianmingPitossi, Fernando JuanPARKINSONINFLAMMATIONDOPAMINERGIC-PRECURSORSCELL-SURVIVALhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Parkinson’s disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons (DAn) of the nigrostriatal system. Studies in animal models of PD have provided proof of concept that transplantation of DA precursors can relieve parkinsonian symptoms. However, a major limiting factor of this strategy is the poor survival rate of grafted DAn. This could be due to host inflammatory response, among other factors. Our previous results demonstrated a host primary response related to the graft of human dopaminergic precursors (DA14), with an increase of host-MHCII positive cells. Expression of tumor necrosis factor-alpha (TNF-alpha) was also detected on hostED1 positive cells. We aim to study the impact of the proinflammatory environment on DA14 cells and the effect of a TNFalpha inhibitor on an in vitro approach. DA14 cells were exposed to conditioned media (CM) from basal or activated BV2 microglial cells during 4 days. A significant increase in cell death was observed by fluorescence microscopy after Hoechst staining in DA14 cultures exposed with CM from activated microglia (p<0.05). This result was in accordance to a decrease in the number of Tyrosine hydroxylase (TH) positive cells detected by immunofluorescence (p<0.01). Neurite length measurement was performed to evaluate the differentiation process. A decrease in neurite length of TH positive cells was detected in DA14 cultures incubated with CM from activated microglia (p<0.05). In order to study the relevance of TNFalpha, DA14 cells were co-incubated with CM from basal or activated BV2 cells and the TNF-alpha inhibitor, Etanercept. Inhibition of TNF-alpha was able to avoid morphological alterations (p<0.05) and diminution of DA cells (p<0.05). Our results suggest that the pro-inflammatory microenvironment has a negative impact on survival and differentiation of DA14 cells. TNF-alpha inhibition could be an interesting strategy in order to improve survival of DA precursors.Fil: Wenker, Shirley Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Gradaschi, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Farias, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ferrari, Carina Cynthia. Hospital Italiano; ArgentinaFil: Zeng, Xianming. Buck Institute For Research On Aging; Estados UnidosFil: Pitossi, Fernando Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaLXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/174556Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursors; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 1-10025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/PMID/32692316.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:03:36Zoai:ri.conicet.gov.ar:11336/174556instacron: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:34982025-09-03 10:03:36.922CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursors
title Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursors
spellingShingle Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursors
Wenker, Shirley Denise
PARKINSON
INFLAMMATION
DOPAMINERGIC-PRECURSORS
CELL-SURVIVAL
title_short Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursors
title_full Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursors
title_fullStr Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursors
title_full_unstemmed Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursors
title_sort Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursors
dc.creator.none.fl_str_mv Wenker, Shirley Denise
Gradaschi, Victoria
Farias, Maria Isabel
Ferrari, Carina Cynthia
Zeng, Xianming
Pitossi, Fernando Juan
author Wenker, Shirley Denise
author_facet Wenker, Shirley Denise
Gradaschi, Victoria
Farias, Maria Isabel
Ferrari, Carina Cynthia
Zeng, Xianming
Pitossi, Fernando Juan
author_role author
author2 Gradaschi, Victoria
Farias, Maria Isabel
Ferrari, Carina Cynthia
Zeng, Xianming
Pitossi, Fernando Juan
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv PARKINSON
INFLAMMATION
DOPAMINERGIC-PRECURSORS
CELL-SURVIVAL
topic PARKINSON
INFLAMMATION
DOPAMINERGIC-PRECURSORS
CELL-SURVIVAL
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Parkinson’s disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons (DAn) of the nigrostriatal system. Studies in animal models of PD have provided proof of concept that transplantation of DA precursors can relieve parkinsonian symptoms. However, a major limiting factor of this strategy is the poor survival rate of grafted DAn. This could be due to host inflammatory response, among other factors. Our previous results demonstrated a host primary response related to the graft of human dopaminergic precursors (DA14), with an increase of host-MHCII positive cells. Expression of tumor necrosis factor-alpha (TNF-alpha) was also detected on hostED1 positive cells. We aim to study the impact of the proinflammatory environment on DA14 cells and the effect of a TNFalpha inhibitor on an in vitro approach. DA14 cells were exposed to conditioned media (CM) from basal or activated BV2 microglial cells during 4 days. A significant increase in cell death was observed by fluorescence microscopy after Hoechst staining in DA14 cultures exposed with CM from activated microglia (p<0.05). This result was in accordance to a decrease in the number of Tyrosine hydroxylase (TH) positive cells detected by immunofluorescence (p<0.01). Neurite length measurement was performed to evaluate the differentiation process. A decrease in neurite length of TH positive cells was detected in DA14 cultures incubated with CM from activated microglia (p<0.05). In order to study the relevance of TNFalpha, DA14 cells were co-incubated with CM from basal or activated BV2 cells and the TNF-alpha inhibitor, Etanercept. Inhibition of TNF-alpha was able to avoid morphological alterations (p<0.05) and diminution of DA cells (p<0.05). Our results suggest that the pro-inflammatory microenvironment has a negative impact on survival and differentiation of DA14 cells. TNF-alpha inhibition could be an interesting strategy in order to improve survival of DA precursors.
Fil: Wenker, Shirley Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Gradaschi, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Farias, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Ferrari, Carina Cynthia. Hospital Italiano; Argentina
Fil: Zeng, Xianming. Buck Institute For Research On Aging; Estados Unidos
Fil: Pitossi, Fernando Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
description Parkinson’s disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons (DAn) of the nigrostriatal system. Studies in animal models of PD have provided proof of concept that transplantation of DA precursors can relieve parkinsonian symptoms. However, a major limiting factor of this strategy is the poor survival rate of grafted DAn. This could be due to host inflammatory response, among other factors. Our previous results demonstrated a host primary response related to the graft of human dopaminergic precursors (DA14), with an increase of host-MHCII positive cells. Expression of tumor necrosis factor-alpha (TNF-alpha) was also detected on hostED1 positive cells. We aim to study the impact of the proinflammatory environment on DA14 cells and the effect of a TNFalpha inhibitor on an in vitro approach. DA14 cells were exposed to conditioned media (CM) from basal or activated BV2 microglial cells during 4 days. A significant increase in cell death was observed by fluorescence microscopy after Hoechst staining in DA14 cultures exposed with CM from activated microglia (p<0.05). This result was in accordance to a decrease in the number of Tyrosine hydroxylase (TH) positive cells detected by immunofluorescence (p<0.01). Neurite length measurement was performed to evaluate the differentiation process. A decrease in neurite length of TH positive cells was detected in DA14 cultures incubated with CM from activated microglia (p<0.05). In order to study the relevance of TNFalpha, DA14 cells were co-incubated with CM from basal or activated BV2 cells and the TNF-alpha inhibitor, Etanercept. Inhibition of TNF-alpha was able to avoid morphological alterations (p<0.05) and diminution of DA cells (p<0.05). Our results suggest that the pro-inflammatory microenvironment has a negative impact on survival and differentiation of DA14 cells. TNF-alpha inhibition could be an interesting strategy in order to improve survival of DA precursors.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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status_str publishedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/174556
Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursors; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 1-1
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/174556
identifier_str_mv Role of pro-inflammatory factors on the survival and differentiation of dopaminergic precursors; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2019; 1-1
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/PMID/32692316.pdf
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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