| Autor: |
Bismark Gatica-Garcia, Michael J Bannon, Irma Alicia Martínez-Dávila, Luis O Soto-Rojas, David Reyes-Corona, Lourdes Escobedo, Minerva Maldonado-Berny, ME Gutierrez-Castillo, Armando J Espadas-Alvarez, Manuel A Fernandez-Parrilla, Juan U Mascotte-Cruz, CP Rodríguez-Oviedo, Irais E Valenzuela-Arzeta, Claudia Luna-Herrera, Francisco E Lopez-Salas, Jaime Santoyo-Salazar, Daniel Martinez-Fong |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Neural Regeneration Research, Vol 19, Iss 9, Pp 2057-2067 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1673-5374 |
| DOI: |
10.4103/1673-5374.391190 |
| Popis: |
[INLINE:1] Parkinsonism by unilateral, intranigral β-sitosterol β-D-glucoside administration in rats is distinguished in that the α-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time, thus replicating several clinical features of Parkinson's disease, a typical α-synucleinopathy. As Nurr1 represses α-synuclein, we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateral β-sitosterol β-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection. This study found that rNurr1-V5 expression but not that of the green fluorescent protein (the negative control) reduced β-sitosterol β-D-glucoside-induced neuropathology. Accordingly, a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum. In addition, tyrosine hydroxylase-positive cells displayed less senescence marker β-galactosidase and more neuron-cytoskeleton marker βIII-tubulin and brain-derived neurotrophic factor. A significant decrease in activated microglia (positive to ionized calcium-binding adaptor molecule 1) and neurotoxic astrocytes (positive to glial fibrillary acidic protein and complement component 3) and increased neurotrophic astrocytes (positive to glial fibrillary acidic protein and S100 calcium-binding protein A10) also occurred in the substantia nigra. These effects followed the bilateral reduction in α-synuclein aggregates in the nigrostriatal system, improving sensorimotor behavior. Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration (senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells), neuroinflammation (activated microglia, neurotoxic astrocytes), α-synuclein aggregation, and sensorimotor deficits. Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect, supporting its potential clinical use in the treatment of Parkinson's disease. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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