Neurotensin-polyplex-mediated brain-derived neurotrophic factor gene delivery into nigral dopamine neurons prevents nigrostriatal degeneration in a rat model of early Parkinson's disease

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dc.contributor.affiliationDepartamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F 07360, Mexico
dc.contributor.emaildmartine@fisio.cinvestav.mx
dc.creatorHernandez-Chan, Nancy G.es_ES
dc.creatorBannon, Michael J.es_ES
dc.creatorOrozco-Barrios, Carlos E.es_ES
dc.creatorEscobedo, Lourdeses_ES
dc.creatorZamudio, Sergioes_ES
dc.creatorCruz, Fidel De laes_ES
dc.creatorGongora-Alfaro, Jose L.es_ES
dc.creatorArmendáriz-Borunda, Juanes_ES
dc.creatorReyes-Corona, Davides_ES
dc.creatorEspadas-Alvarez, Armando J.es_ES
dc.creatorFlores-Martínez, Yazmin M.es_ES
dc.creatorAyala-Davila, Josees_ES
dc.creatorHernandez-Gutierrez, Maria E.es_ES
dc.creatorPavón, Lenines_ES
dc.creatorGarcía-Villegas, Refugioes_ES
dc.creatorNadella, Rasajnaes_ES
dc.creatorMartinez-Fong, Danieles_ES
dc.date2015
dc.date.accessioned2025-09-11T19:36:37Z
dc.date.accessioned2026-03-27T15:32:37Z
dc.date.available2025-09-11T19:36:37Z
dc.date.issued2015
dc.date.published2015
dc.descriptionBackground: The neurotrophin Brain-Derived Neurotrophic Factor (BDNF) influences nigral dopaminergic neurons via autocrine and paracrine mechanisms. The reduction of BDNF expression in Parkinson's disease substantia nigra (SN) might contribute to the death of dopaminergic neurons because inhibiting BDNF expression in the SN causes parkinsonism in the rat. This study aimed to demonstrate that increasing BDNF expression in dopaminergic neurons of rats with one week of 6-hydroxydopamine lesion recovers from parkinsonism. The plasmids phDAT-BDNF-flag and phDAT-EGFP, coding for enhanced green fluorescent protein, were transfected using neurotensin (NTS)-polyplex, which enables delivery of genes into the dopaminergic neurons via neurotensin-receptor type 1 (NTSR1) internalization. Results: Two weeks after transfections, RT-PCR and immunofluorescence techniques showed that the residual dopaminergic neurons retain NTSR1 expression and susceptibility to be transfected by the NTS-polyplex. phDAT-BDNF-flag transfection did not increase dopaminergic neurons, but caused 7-fold increase in dopamine fibers within the SN and 5-fold increase in innervation and dopamine levels in the striatum. These neurotrophic effects were accompanied by a significant improvement in motor behavior. Conclusions: NTS-polyplex-mediated BDNF overexpression in dopaminergic neurons has proven to be effective to remit hemiparkinsonism in the rat. This BDNF gene therapy might be helpful in the early stage of Parkinson's disease.es_ES
dc.formatPDFes_ES
dc.identifier.doi10.1186/s12929-015-0166-7
dc.identifier.eissn1423-0127
dc.identifier.issn1021-7770
dc.identifier.organizacionInstituto Nacional de Psiquiatría Ramón de la Fuente Muñiz
dc.identifier.placeInglaterra
dc.identifier.urihttps://doi.org/10.1186/s12929-015-0166-7
dc.identifier.urihttps://repositorio.inprf.gob.mx/handle/123456789/8413
dc.language.isoenges_ES
dc.publisherBioMed Centrales_ES
dc.relation22:59
dc.relation.jnabreviadoJ BIOMED SCI
dc.relation.journalJournal of Biomedical Science
dc.rightsAcceso Cerradoes_ES
dc.subject.kwNeurorestoration
dc.subject.kwNeurodegeneration
dc.subject.kwParkinson’s disease
dc.subject.kwGene therapy
dc.subject.kwNeurotrophic therapy
dc.titleNeurotensin-polyplex-mediated brain-derived neurotrophic factor gene delivery into nigral dopamine neurons prevents nigrostriatal degeneration in a rat model of early Parkinson's diseasees_ES
dc.typeArtículoes_ES

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