Ghrelin antagonizes MPTP-induced neurotoxicity to the dopaminergic neurons in mouse substantia nigra
Abstract
Ghrelin, a stomach-derived hormone which induces growth hormone release and promotes positive energy balance, has been reported to inhibit cell apoptosis in endotheliocytes, osteoblasts and cardiocytes. Recent evidence has shown that ghrelin can also inhibit neuronal apoptosis of the hypothalamus and the hippocampus. However, little is known about the effects of ghrelin on the substantia nigra pars compacta (SNpc) neurons in which ghrelin's receptor, growth hormone secretagogue receptor (GHSR)-1a, is highly expressed. In the present study, we investigated whether ghrelin could protect nigral dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. We observed that ghrelin, acting through GHS-R 1a, inhibited MPTP-induced dopaminergic neuronal loss in the SNpc as well as dopamine depletion in the striatum. Ghrelin could also reverse the down-regulated the expression of Bcl-2, up-regulated the expression of Bax, and caspase-3 activation caused by MPTP. This study demonstrated that ghrelin might be a potential protector of dopaminergic neurons in a therapeutic strategy for Parkinson's disease.
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The beneficial effects of ghrelin in PD models are attributed to its ability to promote autophagy, enhance mitochondrial biogenesis and bioenergetics, mitigate neuroinflammation, and inhibit apoptosis.
“These beneficial effects are attributed to its ability to promote autophagy, enhance mitochondrial biogenesis and bioenergetics, mitigate neuroinflammation, and inhibit apoptosis.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [566]
Ghrelin has neuroprotective effects in multiple rodent models of PD, including MPTP-induced PD mice, 6-OHDA-induced PD rats, and A53T α-synuclein transgenic mice.
“accumulating evidence has demonstrated the neuroprotective effects of ghrelin in multiple rodent models of PD, including MPTP-induced PD mice”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [566]
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- Authors
- Jiang, H., Li, L.-J., Wang, J., & Xie, J.-X.
- Affiliations
- Qingdao University (CN)
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 212
- Issue
- 2
- Pages
- 532-537
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2010566714
- Cited by
- 144
- References
- 42
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 9 · 2023: 3 · 2022: 10 · 2021: 9 · 2020: 13 · 2019: 4 · 2018: 5 · 2017: 18 · 2016: 8 · 2015: 8 · 2014: 10 · 2013: 14 · 2012: 6
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30770757)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- ghrelin, MPTP-induced neurotoxicity, dopaminergic neurons, substantia nigra pars compacta, growth hormone secretagogue receptor 1a, Parkinson's disease, neuronal apoptosis, Bcl-2, Bax, caspase-3, dopamine depletion, neuroprotection
- MeSH terms
- Analysis of Variance, Animals, Disease Models, Animal, Dopamine, Dose-Response Relationship, Drug, Drug Interactions, Male, Mice, Inbred C57BL, Neurons, Substantia Nigra, Tyrosine 3-Monooxygenase, Down-Regulation, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Chi-Square Distribution, Proto-Oncogene Proteins c-bcl-2, MPTP Poisoning, Mice, Caspase 3, Ghrelin, Receptors, Ghrelin
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