| Autor: |
Manuel A Fernandez-Parrilla, David Reyes-Corona, Yazmin M Flores-Martinez, Rasajna Nadella, Michael J Bannon, Lourdes Escobedo, Minerva Maldonado-Berny, Jaime Santoyo-Salazar, Luis O Soto-Rojas, Claudia Luna-Herrera, Jose Ayala-Davila, Juan A Gonzalez-Barrios, Gonzalo Flores, Maria E Gutierrez-Castillo, Armando J Espadas-Alvarez, Irma A Martínez-Dávila, Porfirio Nava, Daniel Martinez-Fong |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Neural Regeneration Research, Vol 17, Iss 4, Pp 854-866 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1673-5374 |
| DOI: |
10.4103/1673-5374.321001 |
| Popis: |
Overexpression of neurotrophic factors in nigral dopamine neurons is a promising approach to reverse neurodegeneration of the nigrostriatal dopamine system, a hallmark in Parkinson’s disease. The human cerebral dopamine neurotrophic factor (hCDNF) has recently emerged as a strong candidate for Parkinson’s disease therapy. This study shows that hCDNF expression in dopamine neurons using the neurotensin-polyplex nanoparticle system reverses 6-hydroxydopamine-induced morphological, biochemical, and behavioral alterations. Three independent electron microscopy techniques showed that the neurotensin-polyplex nanoparticles containing the hCDNF gene, ranging in size from 20 to 150 nm, enabled the expression of a secretable hCDNF in vitro. Their injection in the substantia nigra compacta on day 21 after the 6-hydroxydopamine lesion resulted in detectable hCDNF in dopamine neurons, whose levels remained constant throughout the study in the substantia nigra compacta and striatum. Compared with the lesioned group, tyrosine hydroxylase-positive (TH+) nigral cell population and TH+ fiber density rose in the substantia nigra compacta and striatum after hCDNF transfection. An increase in βIII-tubulin and growth-associated protein 43 phospho-S41 (GAP43p) followed TH+ cell recovery, as well as dopamine and its catabolite levels. Partial reversal (80%) of drug-activated circling behavior and full recovery of spontaneous motor and non-motor behavior were achieved. Brain-derived neurotrophic factor recovery in dopamine neurons that also occurred suggests its participation in the neurotrophic effects. These findings support the potential of nanoparticle-mediated hCDNF gene delivery to develop a disease-modifying treatment against Parkinson’s disease. The Institutional Animal Care and Use Committee of Centro de Investigación y de Estudios Avanzados approved our experimental procedures for animal use (authorization No. 162-15) on June 9, 2019. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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