Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson’s Disease
In Parkinson’s disease (PD), progressive degeneration of nigrostriatal innervation leads to atrophy and loss of dendritic spines of striatal medium spiny neurons (MSNs). The loss disrupts corticostriatal transmission, impairs motor behavior, and produces nonmotor symptoms. Nigral neurons express bra...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2024/3885451 |
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| author | Alina Benítez-Castañeda Verónica Anaya-Martínez Armando de Jesús Espadas-Alvarez Ana Luisa Gutierrez-Váldez Luis Fernando Razgado-Hernández Patricia Emmanuelle Reyna-Velazquez Liz Quintero-Macias Daniel Martínez-Fong Benjamín Florán-Garduño Jorge Aceves |
| author_facet | Alina Benítez-Castañeda Verónica Anaya-Martínez Armando de Jesús Espadas-Alvarez Ana Luisa Gutierrez-Váldez Luis Fernando Razgado-Hernández Patricia Emmanuelle Reyna-Velazquez Liz Quintero-Macias Daniel Martínez-Fong Benjamín Florán-Garduño Jorge Aceves |
| author_sort | Alina Benítez-Castañeda |
| collection | DOAJ |
| description | In Parkinson’s disease (PD), progressive degeneration of nigrostriatal innervation leads to atrophy and loss of dendritic spines of striatal medium spiny neurons (MSNs). The loss disrupts corticostriatal transmission, impairs motor behavior, and produces nonmotor symptoms. Nigral neurons express brain-derived neurotropic factor (BDNF) and dopamine D3 receptors, both protecting the dopamine neurons and the spines of MSNs. To restore motor and nonmotor symptoms to normality, we assessed a combined therapy in a bilateral rat Parkinson’s model, with only 30% of surviving neurons. The preferential D3 agonist pramipexole (PPX) was infused for four ½ months via mini-osmotic pumps and one month after PPX initiation; the BDNF-gene was transfected into the surviving nigral cells using the nonviral transfection NTS-polyplex vector. Overexpression of the BDNF-gene associated with continuous PPX infusion restored motor coordination, balance, normal gait, and working memory. Recovery was also related to the restoration of the average number of dendritic spines of the striatal projection neurons and the number of TH-positive neurons of the substantia nigra and ventral tegmental area. These positive results could pave the way for further clinical research into this promising therapy. |
| format | Article |
| id | doaj-art-2ef3c2e6a56a437386b0f37006d97dba |
| institution | Kabale University |
| issn | 2042-0080 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-2ef3c2e6a56a437386b0f37006d97dba2025-02-03T01:29:31ZengWileyParkinson's Disease2042-00802024-01-01202410.1155/2024/3885451Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson’s DiseaseAlina Benítez-Castañeda0Verónica Anaya-Martínez1Armando de Jesús Espadas-Alvarez2Ana Luisa Gutierrez-Váldez3Luis Fernando Razgado-Hernández4Patricia Emmanuelle Reyna-Velazquez5Liz Quintero-Macias6Daniel Martínez-Fong7Benjamín Florán-Garduño8Jorge Aceves9Center for Research and Advanced Studies of the National Polytechnic InstituteCenter for Research in Health SciencesCenter for Research and Advanced Studies of the National Polytechnic InstituteNeuromorphology LaboratoryCenter for Research in Health SciencesCenter for Research and Advanced Studies of the National Polytechnic InstituteCenter for Research and Advanced Studies of the National Polytechnic InstituteCenter for Research and Advanced Studies of the National Polytechnic InstituteCenter for Research and Advanced Studies of the National Polytechnic InstituteCenter for Research and Advanced Studies of the National Polytechnic InstituteIn Parkinson’s disease (PD), progressive degeneration of nigrostriatal innervation leads to atrophy and loss of dendritic spines of striatal medium spiny neurons (MSNs). The loss disrupts corticostriatal transmission, impairs motor behavior, and produces nonmotor symptoms. Nigral neurons express brain-derived neurotropic factor (BDNF) and dopamine D3 receptors, both protecting the dopamine neurons and the spines of MSNs. To restore motor and nonmotor symptoms to normality, we assessed a combined therapy in a bilateral rat Parkinson’s model, with only 30% of surviving neurons. The preferential D3 agonist pramipexole (PPX) was infused for four ½ months via mini-osmotic pumps and one month after PPX initiation; the BDNF-gene was transfected into the surviving nigral cells using the nonviral transfection NTS-polyplex vector. Overexpression of the BDNF-gene associated with continuous PPX infusion restored motor coordination, balance, normal gait, and working memory. Recovery was also related to the restoration of the average number of dendritic spines of the striatal projection neurons and the number of TH-positive neurons of the substantia nigra and ventral tegmental area. These positive results could pave the way for further clinical research into this promising therapy.http://dx.doi.org/10.1155/2024/3885451 |
| spellingShingle | Alina Benítez-Castañeda Verónica Anaya-Martínez Armando de Jesús Espadas-Alvarez Ana Luisa Gutierrez-Váldez Luis Fernando Razgado-Hernández Patricia Emmanuelle Reyna-Velazquez Liz Quintero-Macias Daniel Martínez-Fong Benjamín Florán-Garduño Jorge Aceves Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson’s Disease Parkinson's Disease |
| title | Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson’s Disease |
| title_full | Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson’s Disease |
| title_fullStr | Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson’s Disease |
| title_full_unstemmed | Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson’s Disease |
| title_short | Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson’s Disease |
| title_sort | transfection of the bdnf gene in the surviving dopamine neurons in conjunction with continuous administration of pramipexole restores normal motor behavior in a bilateral rat model of parkinson s disease |
| url | http://dx.doi.org/10.1155/2024/3885451 |
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