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.

Autor: Hernandez-Chan NG; Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. nhernandez@upsrj.edu.mx., Bannon MJ; Department of Pharmacology, Wayne State University School of Medicine, 540 E Canfield Ave, 3355 Scott Hall, Detroit, MI, 48201, USA. mbannon@med.wayne.edu., Orozco-Barrios CE; Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. crls2878@gmail.com., Escobedo L; Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. escobedo@fisio.cinvestv.mx., Zamudio S; Escuela Nacional de Ciencias Biológicas, IPN, Wilfrido Massieu s/n, México D.F, 07738, Mexico. zrzamudio@hotmail.com., De la Cruz F; Escuela Nacional de Ciencias Biológicas, IPN, Wilfrido Massieu s/n, México D.F, 07738, Mexico. flacruz90@hotmail.com., Gongora-Alfaro JL; Departamento de Neurociencias, Centro de Investigaciones Regionales 'Dr. Hideyo Noguchi', Universidad de Yucatán, Av. Itzaes # 490 x 59-A, Mérida, Yucatán, 97000, Mexico. galfaro@uady.mx., Armendáriz-Borunda J; Institute for Molecular Biology and Gene Therapy, Department of Molecular Biology and Genomics, University of Guadalajara, Sierra Mojada # 950, Guadalajara, Jalisco, 44281, Mexico. armdbo@gmail.com., Reyes-Corona D; Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. davidreyescorona@gmail.com., Espadas-Alvarez AJ; Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. armandoespadas1@gmail.com., Flores-Martínez YM; Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. ymfloresm@hotmail.com., Ayala-Davila J; Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. josead65@gmail.com., Hernandez-Gutierrez ME; Department of Psychoimmunology, National Institute of Psychiatry 'Ramón de la Fuente', Calzada México Xochimilco # 101, México D.F, 14370, Mexico. drosoph2001@yahoo.com.mx., Pavón L; Department of Psychoimmunology, National Institute of Psychiatry 'Ramón de la Fuente', Calzada México Xochimilco # 101, México D.F, 14370, Mexico. lkuriaki@gmail.com., García-Villegas R; Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. rgarciav@fisio.cinvestav.mx., Nadella R; Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. rasagna.s@gmail.com.; Program de doctorado en Nanociencias and Nanotecnología, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. rasagna.s@gmail.com., Martinez-Fong D; Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. dmartine@fisio.cinvestav.mx.; Program de doctorado en Nanociencias and Nanotecnología, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. dmartine@fisio.cinvestav.mx.
Jazyk: angličtina
Zdroj: Journal of biomedical science [J Biomed Sci] 2015 Jul 22; Vol. 22, pp. 59. Date of Electronic Publication: 2015 Jul 22.
DOI: 10.1186/s12929-015-0166-7
Abstrakt: Background: 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.
Databáze: MEDLINE
Externí odkaz: