Early expression of monomeric and oligomeric alpha-synuclein and reduction of tyrosine hydroxylase following intranigral injection of lipopolysaccharide.

Autor: Lomeli-Lepe AK; Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Camino Ing. Ramón Padilla Sánchez #2100, Predio Las Agujas, Zapopan, Jalisco, México., López-Pérez SJ; Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Camino Ing. Ramón Padilla Sánchez #2100, Predio Las Agujas, Zapopan, Jalisco, México. silvia.lperez@academicos.udg.mx., Castañeda-Cabral JL; Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Camino Ing. Ramón Padilla Sánchez #2100, Predio Las Agujas, Zapopan, Jalisco, México., Ureña-Guerrero ME; Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Camino Ing. Ramón Padilla Sánchez #2100, Predio Las Agujas, Zapopan, Jalisco, México.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2024 Sep 19; Vol. 51 (1), pp. 996. Date of Electronic Publication: 2024 Sep 19.
DOI: 10.1007/s11033-024-09935-2
Abstrakt: Background: The insoluble tangles of alpha-synuclein (α-syn) protein in the nigrostriatal circuit, characteristic of synucleinopathy, originate from low molecular weight oligomers, whose appearance and dissemination are related to neuroinflammation. These oligomeric forms of α-syn are considered highly cytotoxic but transient, so knowing the timing in which they appear remains challenging. Therefore, this study aimed to analyze the abundance of oligomeric forms of α-syn and tyrosine hydroxylase (TH) between 3 and 7 days after inducing neuroinflammation with lipopolysaccharide (LPS).
Methods and Results: LPS (2.5 µg/2.5 µL) was stereotaxically injected in the substantia nigra (SN) of adult male Wistar rats, which were sacrificed 3, 5 and 7 days after this intervention. The brains were processed for semi quantitative Western blot, along with brains from control and sham animals. Our results show an increased expression of α-syn monomer (15 kDa) only 3 days after LPS infusion, and the formation of 50 KDa and 60 kDa α-syn oligomers in the SN and striatum (STR) between 3 and 7 days after LPS infusion. Furthermore, the presence of these oligomers was accompanied by a decrease in the expression of nigral TH.
Conclusion: These findings highlight the rapidity with which potentially toxic forms of α-syn appear in the nigrostriatal circuit after a neuroinflammatory challenge, in addition to allowing us to identify specific oligomers and a temporal relation with neurodegeneration of TH-positive cells. Knowledge of the timing and location in which these small oligomers appear is essential to developing therapeutic strategies to prevent its formation.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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