TY - JOUR
T1 - 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
AU - Hernandez-Chan, Nancy G.
AU - Bannon, Michael J.
AU - Orozco-Barrios, Carlos E.
AU - Escobedo, Lourdes
AU - Zamudio, Sergio
AU - De La Cruz, Fidel
AU - Gongora-Alfaro, Jose L.
AU - Armendáriz-Borunda, Juan
AU - Reyes-Corona, David
AU - Espadas-Alvarez, Armando J.
AU - Flores-Martínez, Yazmin M.
AU - Ayala-Davila, Jose
AU - Hernandez-Gutierrez, Maria E.
AU - Pavón, Lenin
AU - García-Villegas, Refugio
AU - Nadella, Rasajna
AU - Martinez-Fong, Daniel
N1 - Publisher Copyright:
© 2015 Hernandez-Chan et al.
PY - 2015/7/22
Y1 - 2015/7/22
N2 - 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 su, D.Ftantia 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.
AB - 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 su, D.Ftantia 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.
KW - Gene therapy
KW - Neurodegeneration
KW - Neurorestoration
KW - Neurotrophic therapy
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=84937394030&partnerID=8YFLogxK
U2 - 10.1186/s12929-015-0166-7
DO - 10.1186/s12929-015-0166-7
M3 - Artículo
SN - 1021-7770
VL - 22
JO - Journal of Biomedical Science
JF - Journal of Biomedical Science
IS - 1
M1 - 59
ER -