JM-20 administration to animals with lesion of the nigrostriatal dopamine pathway induced by 6-hydroxydopamine, partially reverses motor damage and oxidative stress

Fonseca Fonseca, L. A.; Tano Portuondo, L. R.; Ramirez-Sanchez, J.; Pavon Fuentes, N.; Mondelo Rodriguez, A.; Amaral da Silva, V. D.; Lima Costa, S.; Nunez-Figueredo, Y.

doi:10.1101/2024.07.30.605870

bioRxiv · 10.1101/2024.07.30.605870

JM-20 administration to animals with lesion of the nigrostriatal dopamine pathway induced by 6-hydroxydopamine, partially reverses motor damage and oxidative stress

Fonseca Fonseca, L. A.·Tano Portuondo, L. R.·Ramirez-Sanchez, J.·Pavon Fuentes, N.·Mondelo Rodriguez, A.·Amaral da Silva, V. D.·Lima Costa, S.·Nunez-Figueredo, Y.

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Abstract

Previous studies have shown that JM-20, a new chemical hybrid molecule, protects against rotenone and 6-hydroxydopamine neurotoxicity. Also, we demonstrated that JM-20 blocks the formation of toxic alpha-synuclein aggregated species and aminochrome cytotoxicity. The present study sought to determine the neuroprotective property of JM-20 in animals with a partial lesion of the nigrostriatal dopamine pathway induced by 6-hydroxydopamine (6-OHDA). For in vivo studies, adult male Wistar rats were lesioned in the right substantia nigra pars compacta (SNpc) with 6-OHDA administration. Fifteen days after surgery, the animals asymmetry levels were assessed. Those with asymmetry values higher than 50% were divided into two groups: animals that did not receive any treatment and those that were administered with JM-20 (40 mg/kg, intragastric via gavage) for 27 days. Every seven days, the asymmetry values of the animals were analyzed until day 42 after the surgery. At the end of the experiment, the animals were euthanized and the SNpc and striatum were taken out for the analysis of oxidative stress. Our results reveal a behavioral function progressively recovered in the JM-20-treated animals, diminishing the percentage of motor asymmetry. Also, it improves some oxidative stress markers in the SNpc and the striatum of these animals. Our study provides the preclinical evidence to support the long-term neuroprotective potential of JM-20 in 6-OHDA hemiparkinson rat model, pointing out to its possible use as a disease-modifying agent in PD.

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Fonseca Fonseca, L. A., Tano Portuondo, L. R., Ramirez-Sanchez, J., Pavon Fuentes, N., Mondelo Rodriguez, A., Amaral da Silva, V. D., Lima Costa, S., Nunez-Figueredo, Y.. 2024-08-01. JM-20 administration to animals with lesion of the nigrostriatal dopamine pathway induced by 6-hydroxydopamine, partially reverses motor damage and oxidative stress. https://doi.org/10.1101/2024.07.30.605870

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