Cerebral dopamine neurotrophic factor transfection in dopamine neurons using neurotensin-polyplex nanoparticles reverses 6-hydroxydopamine-induced nigrostriatal neurodegeneration
| العنوان: | Cerebral dopamine neurotrophic factor transfection in dopamine neurons using neurotensin-polyplex nanoparticles reverses 6-hydroxydopamine-induced nigrostriatal neurodegeneration |
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| المؤلفون: | Manuel A. Fernandez-Parrilla, Minerva Maldonado-Berny, Yazmin M. Flores-Martinez, Jose Ayala-Davila, David Reyes-Corona, Claudia Luna-Herrera, Daniel Martinez-Fong, Rasajna Nadella, Maria E. Gutierrez-Castillo, Jaime Santoyo-Salazar, Luis O Soto-Rojas, Juan Antonio González-Barrios, Irma A Martínez-Dávila, Gonzalo Flores, Michael J. Bannon, Armando J. Espadas-Alvarez, Lourdes Escobedo, Porfirio Nava |
| المصدر: | Neural Regeneration Research Neural Regeneration Research, Vol 17, Iss 4, Pp 854-866 (2022) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | medicine.medical_specialty, neurotrophic therapy, Parkinson's disease, neuronal cytoskeleton, Substantia nigra, Striatum, axonal growth, brain-derived neurotrophic factor, gene delivery, nanoparticles, neuritogenesis, neuroregeneration, neurorestoration, parkinson’s disease, reinnervation, substantia nigra, Developmental Neuroscience, Neurotrophic factors, Dopamine, Internal medicine, medicine, RC346-429, Cerebral dopamine neurotrophic factor, Brain-derived neurotrophic factor, Chemistry, Pars compacta, medicine.disease, Endocrinology, nervous system, Neurology. Diseases of the nervous system, medicine.drug, Research Article |
| الوصف: | 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. |
| تدمد: | 1673-5374 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e0aa93df8088ef94931d7128ad16419e https://pubmed.ncbi.nlm.nih.gov/34472486 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e0aa93df8088ef94931d7128ad16419e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16735374 |
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