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The Transfection of BDNF to Dopamine Neurons Potentiates the Effect of Dopamine D3 Receptor Agonist Recovering the Striatal Innervation, Dendritic Spines and Motor Behavior in an Aged Rat Model of Parkinson’s Disease

The progressive degeneration of the dopamine neurons of the pars compacta of substantia nigra and the consequent loss of the dopamine innervation of the striatum leads to the impairment of motor behavior in Parkinson’s disease. Accordingly, an efficient therapy of the disease should protect and rege...

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Autores principales: Razgado-Hernandez, Luis F., Espadas-Alvarez, Armando J., Reyna-Velazquez, Patricia, Sierra-Sanchez, Arturo, Anaya-Martinez, Veronica, Jimenez-Estrada, Ismael, Bannon, Michael J., Martinez-Fong, Daniel, Aceves-Ruiz, Jorge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332861/
https://www.ncbi.nlm.nih.gov/pubmed/25693197
http://dx.doi.org/10.1371/journal.pone.0117391
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author Razgado-Hernandez, Luis F.
Espadas-Alvarez, Armando J.
Reyna-Velazquez, Patricia
Sierra-Sanchez, Arturo
Anaya-Martinez, Veronica
Jimenez-Estrada, Ismael
Bannon, Michael J.
Martinez-Fong, Daniel
Aceves-Ruiz, Jorge
author_facet Razgado-Hernandez, Luis F.
Espadas-Alvarez, Armando J.
Reyna-Velazquez, Patricia
Sierra-Sanchez, Arturo
Anaya-Martinez, Veronica
Jimenez-Estrada, Ismael
Bannon, Michael J.
Martinez-Fong, Daniel
Aceves-Ruiz, Jorge
author_sort Razgado-Hernandez, Luis F.
collection PubMed
description The progressive degeneration of the dopamine neurons of the pars compacta of substantia nigra and the consequent loss of the dopamine innervation of the striatum leads to the impairment of motor behavior in Parkinson’s disease. Accordingly, an efficient therapy of the disease should protect and regenerate the dopamine neurons of the substantia nigra and the dopamine innervation of the striatum. Nigral neurons express Brain Derived Neurotropic Factor (BDNF) and dopamine D3 receptors, both of which protect the dopamine neurons. The chronic activation of dopamine D3 receptors by their agonists, in addition, restores, in part, the dopamine innervation of the striatum. Here we explored whether the over-expression of BDNF by dopamine neurons potentiates the effect of the activation of D3 receptors restoring nigrostriatal innervation. Twelve-month old Wistar rats were unilaterally injected with 6-hydroxydopamine into the striatum. Five months later, rats were treated with the D3 agonist 7-hydroxy-N,N-di-n-propy1-2-aminotetralin (7-OH-DPAT) administered i.p. during 4½ months via osmotic pumps and the BDNF gene transfection into nigral cells using the neurotensin-polyplex nanovector (a non-viral transfection) that selectively transfect the dopamine neurons via the high-affinity neurotensin receptor expressed by these neurons. Two months after the withdrawal of 7-OH-DPAT when rats were aged (24 months old), immunohistochemistry assays were made. The over-expression of BDNF in rats receiving the D3 agonist normalized gait and motor coordination; in addition, it eliminated the muscle rigidity produced by the loss of dopamine. The recovery of motor behavior was associated with the recovery of the nigral neurons, the dopamine innervation of the striatum and of the number of dendritic spines of the striatal neurons. Thus, the over-expression of BDNF in dopamine neurons associated with the chronic activation of the D3 receptors appears to be a promising strategy for restoring dopamine neurons in Parkinson’s disease.
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spelling pubmed-43328612015-02-24 The Transfection of BDNF to Dopamine Neurons Potentiates the Effect of Dopamine D3 Receptor Agonist Recovering the Striatal Innervation, Dendritic Spines and Motor Behavior in an Aged Rat Model of Parkinson’s Disease Razgado-Hernandez, Luis F. Espadas-Alvarez, Armando J. Reyna-Velazquez, Patricia Sierra-Sanchez, Arturo Anaya-Martinez, Veronica Jimenez-Estrada, Ismael Bannon, Michael J. Martinez-Fong, Daniel Aceves-Ruiz, Jorge PLoS One Research Article The progressive degeneration of the dopamine neurons of the pars compacta of substantia nigra and the consequent loss of the dopamine innervation of the striatum leads to the impairment of motor behavior in Parkinson’s disease. Accordingly, an efficient therapy of the disease should protect and regenerate the dopamine neurons of the substantia nigra and the dopamine innervation of the striatum. Nigral neurons express Brain Derived Neurotropic Factor (BDNF) and dopamine D3 receptors, both of which protect the dopamine neurons. The chronic activation of dopamine D3 receptors by their agonists, in addition, restores, in part, the dopamine innervation of the striatum. Here we explored whether the over-expression of BDNF by dopamine neurons potentiates the effect of the activation of D3 receptors restoring nigrostriatal innervation. Twelve-month old Wistar rats were unilaterally injected with 6-hydroxydopamine into the striatum. Five months later, rats were treated with the D3 agonist 7-hydroxy-N,N-di-n-propy1-2-aminotetralin (7-OH-DPAT) administered i.p. during 4½ months via osmotic pumps and the BDNF gene transfection into nigral cells using the neurotensin-polyplex nanovector (a non-viral transfection) that selectively transfect the dopamine neurons via the high-affinity neurotensin receptor expressed by these neurons. Two months after the withdrawal of 7-OH-DPAT when rats were aged (24 months old), immunohistochemistry assays were made. The over-expression of BDNF in rats receiving the D3 agonist normalized gait and motor coordination; in addition, it eliminated the muscle rigidity produced by the loss of dopamine. The recovery of motor behavior was associated with the recovery of the nigral neurons, the dopamine innervation of the striatum and of the number of dendritic spines of the striatal neurons. Thus, the over-expression of BDNF in dopamine neurons associated with the chronic activation of the D3 receptors appears to be a promising strategy for restoring dopamine neurons in Parkinson’s disease. Public Library of Science 2015-02-18 /pmc/articles/PMC4332861/ /pubmed/25693197 http://dx.doi.org/10.1371/journal.pone.0117391 Text en © 2015 Razgado-Hernandez et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Razgado-Hernandez, Luis F.
Espadas-Alvarez, Armando J.
Reyna-Velazquez, Patricia
Sierra-Sanchez, Arturo
Anaya-Martinez, Veronica
Jimenez-Estrada, Ismael
Bannon, Michael J.
Martinez-Fong, Daniel
Aceves-Ruiz, Jorge
The Transfection of BDNF to Dopamine Neurons Potentiates the Effect of Dopamine D3 Receptor Agonist Recovering the Striatal Innervation, Dendritic Spines and Motor Behavior in an Aged Rat Model of Parkinson’s Disease
title The Transfection of BDNF to Dopamine Neurons Potentiates the Effect of Dopamine D3 Receptor Agonist Recovering the Striatal Innervation, Dendritic Spines and Motor Behavior in an Aged Rat Model of Parkinson’s Disease
title_full The Transfection of BDNF to Dopamine Neurons Potentiates the Effect of Dopamine D3 Receptor Agonist Recovering the Striatal Innervation, Dendritic Spines and Motor Behavior in an Aged Rat Model of Parkinson’s Disease
title_fullStr The Transfection of BDNF to Dopamine Neurons Potentiates the Effect of Dopamine D3 Receptor Agonist Recovering the Striatal Innervation, Dendritic Spines and Motor Behavior in an Aged Rat Model of Parkinson’s Disease
title_full_unstemmed The Transfection of BDNF to Dopamine Neurons Potentiates the Effect of Dopamine D3 Receptor Agonist Recovering the Striatal Innervation, Dendritic Spines and Motor Behavior in an Aged Rat Model of Parkinson’s Disease
title_short The Transfection of BDNF to Dopamine Neurons Potentiates the Effect of Dopamine D3 Receptor Agonist Recovering the Striatal Innervation, Dendritic Spines and Motor Behavior in an Aged Rat Model of Parkinson’s Disease
title_sort transfection of bdnf to dopamine neurons potentiates the effect of dopamine d3 receptor agonist recovering the striatal innervation, dendritic spines and motor behavior in an aged rat model of parkinson’s disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332861/
https://www.ncbi.nlm.nih.gov/pubmed/25693197
http://dx.doi.org/10.1371/journal.pone.0117391
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