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Neuroprotective Effect of Curcumin on the Nigrostriatal Pathway in a 6-Hydroxydopmine-Induced Rat Model of Parkinson's Disease is Mediated by α7-Nicotinic Receptors.
Int J Mol Sci. 2020 Oct 03; 21(19)IJ

Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic nigrostriatal neurons. Most of the existing pharmacological approaches in PD consider replenishing striatal dopamine. It has been reported that activation of the cholinergic system has neuroprotective effects on dopaminergic neurons, and human α7-nicotinic acetylcholine receptor (α7-nAChR) stimulation may offer a potential therapeutic approach in PD. Our recent in-vitro studies demonstrated that curcumin causes significant potentiation of the function of α7-nAChRs expressed in Xenopus oocytes. In this study, we conducted in vivo experiments to assess the role of the α7-nAChR on the protective effects of curcumin in an animal model of PD. Intra-striatal injection of 6-hydroxydopmine (6-OHDA) was used to induce Parkinsonism in rats. Our results demonstrated that intragastric curcumin treatment (200 mg/kg) significantly improved the abnormal motor behavior and offered neuroprotection against the reduction of dopaminergic neurons, as determined by tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra and caudoputamen. The intraperitoneal administration of the α7-nAChR-selective antagonist methyllycaconitine (1 µg/kg) reversed the neuroprotective effects of curcumin in terms of both animal behavior and TH immunoreactivity. In conclusion, this study demonstrates that curcumin has a neuroprotective effect in a 6-hydroxydopmine (6-OHDA) rat model of PD via an α7-nAChR-mediated mechanism.

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Authors+Show Affiliations

El Nebrisi E
Department of Pharmacology, Dubai Medical College, Dubai Medical University, Dubai 20170, UAE. Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain PO BOX 17666, UAE.
Javed H
Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain PO BOX 17666, UAE.
Ojha SK
Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain PO BOX 17666, UAE.
Oz M
Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain PO BOX 17666, UAE. Department of Pharmacology and Therapeutics, College of Pharmacy, Kuwait University, Kuwait 24923, Kuwait.
Shehab S
Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain PO BOX 17666, UAE.

MeSH

AnimalsCorpus StriatumCurcuminDisease Models, AnimalDopamineDopaminergic NeuronsHumansOxidopamineParkinson DiseaseParkinson Disease, SecondaryRatsSubstantia Nigraalpha7 Nicotinic Acetylcholine Receptor

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33023066

Citation

El Nebrisi, Eslam, et al. "Neuroprotective Effect of Curcumin On the Nigrostriatal Pathway in a 6-Hydroxydopmine-Induced Rat Model of Parkinson's Disease Is Mediated By α7-Nicotinic Receptors." International Journal of Molecular Sciences, vol. 21, no. 19, 2020.
El Nebrisi E, Javed H, Ojha SK, et al. Neuroprotective Effect of Curcumin on the Nigrostriatal Pathway in a 6-Hydroxydopmine-Induced Rat Model of Parkinson's Disease is Mediated by α7-Nicotinic Receptors. Int J Mol Sci. 2020;21(19).
El Nebrisi, E., Javed, H., Ojha, S. K., Oz, M., & Shehab, S. (2020). Neuroprotective Effect of Curcumin on the Nigrostriatal Pathway in a 6-Hydroxydopmine-Induced Rat Model of Parkinson's Disease is Mediated by α7-Nicotinic Receptors. International Journal of Molecular Sciences, 21(19). https://doi.org/10.3390/ijms21197329
El Nebrisi E, et al. Neuroprotective Effect of Curcumin On the Nigrostriatal Pathway in a 6-Hydroxydopmine-Induced Rat Model of Parkinson's Disease Is Mediated By α7-Nicotinic Receptors. Int J Mol Sci. 2020 Oct 3;21(19) PubMed PMID: 33023066.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective Effect of Curcumin on the Nigrostriatal Pathway in a 6-Hydroxydopmine-Induced Rat Model of Parkinson's Disease is Mediated by α7-Nicotinic Receptors. AU - El Nebrisi,Eslam, AU - Javed,Hayate, AU - Ojha,Shreesh K, AU - Oz,Murat, AU - Shehab,Safa, Y1 - 2020/10/03/ PY - 2020/07/19/received PY - 2020/08/05/revised PY - 2020/08/11/accepted PY - 2020/10/7/entrez PY - 2020/10/8/pubmed PY - 2021/2/24/medline KW - 6-OHDA KW - Parkinson’s disease KW - curcumin KW - neuroprotection KW - α7-nAChR JF - International journal of molecular sciences JO - Int J Mol Sci VL - 21 IS - 19 N2 - Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic nigrostriatal neurons. Most of the existing pharmacological approaches in PD consider replenishing striatal dopamine. It has been reported that activation of the cholinergic system has neuroprotective effects on dopaminergic neurons, and human α7-nicotinic acetylcholine receptor (α7-nAChR) stimulation may offer a potential therapeutic approach in PD. Our recent in-vitro studies demonstrated that curcumin causes significant potentiation of the function of α7-nAChRs expressed in Xenopus oocytes. In this study, we conducted in vivo experiments to assess the role of the α7-nAChR on the protective effects of curcumin in an animal model of PD. Intra-striatal injection of 6-hydroxydopmine (6-OHDA) was used to induce Parkinsonism in rats. Our results demonstrated that intragastric curcumin treatment (200 mg/kg) significantly improved the abnormal motor behavior and offered neuroprotection against the reduction of dopaminergic neurons, as determined by tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra and caudoputamen. The intraperitoneal administration of the α7-nAChR-selective antagonist methyllycaconitine (1 µg/kg) reversed the neuroprotective effects of curcumin in terms of both animal behavior and TH immunoreactivity. In conclusion, this study demonstrates that curcumin has a neuroprotective effect in a 6-hydroxydopmine (6-OHDA) rat model of PD via an α7-nAChR-mediated mechanism. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/33023066/Neuroprotective_Effect_of_Curcumin_on_the_Nigrostriatal_Pathway_in_a_6_Hydroxydopmine_Induced_Rat_Model_of_Parkinson's_Disease_is_Mediated_by_α7_Nicotinic_Receptors_ DB - PRIME DP - Unbound Medicine ER -