title: 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.
abstract: 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.
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. nhernandez@upsrj.edu.mx.
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Hernandez-Chan
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, 540 E Canfield Ave, 3355 Scott Hall, Detroit, MI, 48201, USA. mbannon@med.wayne.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bannon
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. crls2878@gmail.com.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Orozco-Barrios
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. escobedo@fisio.cinvestv.mx.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Escobedo
authors.affiliation: Escuela Nacional de Ciencias Biológicas, IPN, Wilfrido Massieu s/n, México D.F, 07738, Mexico. zrzamudio@hotmail.com.
authors.forename: Sergio
authors.initials: S
authors.lastname: Zamudio
authors.affiliation: Escuela Nacional de Ciencias Biológicas, IPN, Wilfrido Massieu s/n, México D.F, 07738, Mexico. flacruz90@hotmail.com.
authors.forename: Fidel
authors.initials: F
authors.lastname: De la Cruz
authors.affiliation: 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.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Gongora-Alfaro
authors.affiliation: 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Armendáriz-Borunda
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. davidreyescorona@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Reyes-Corona
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. armandoespadas1@gmail.com.
authors.forename: Armando J
authors.initials: AJ
authors.lastname: Espadas-Alvarez
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. ymfloresm@hotmail.com.
authors.forename: Yazmin M
authors.initials: YM
authors.lastname: Flores-Martínez
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. josead65@gmail.com.
authors.forename: Jose
authors.initials: J
authors.lastname: Ayala-Davila
authors.affiliation: Department of Psychoimmunology, National Institute of Psychiatry "Ramón de la Fuente", Calzada México Xochimilco # 101, México D.F, 14370, Mexico. drosoph2001@yahoo.com.mx.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Hernandez-Gutierrez
authors.affiliation: Department of Psychoimmunology, National Institute of Psychiatry "Ramón de la Fuente", Calzada México Xochimilco # 101, México D.F, 14370, Mexico. lkuriaki@gmail.com.
authors.forename: Lenin
authors.initials: L
authors.lastname: Pavón
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, Av. Instituto Politécnico Nacional # 2508, México D.F, 07360, Mexico. rgarciav@fisio.cinvestav.mx.
authors.forename: Refugio
authors.initials: R
authors.lastname: García-Villegas
authors.affiliation: 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.
authors.forename: Rasajna
authors.initials: R
authors.lastname: Nadella
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martinez-Fong
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D015316:Genetic Therapy / Q000379:methods; D008297:Male; D009496:Neurotensin / Q000737:chemistry / Q000494:pharmacology; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar; D018028:Receptors, Neurotensin / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D014162:Transfection / Q000379:methods*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin