Abstract
The present study was designed to ascertain the role of naringenin (NGN), a citrus fruit flavanone, against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced α-synuclein (SYN) pathology and neuroinflammation in a mouse model. NGN was administered to C57BL/6J mice once a day for 5 consecutive days prior to the MPTP intoxication. On day 5, 40–50 min after the NGN or vehicle administration, MPTP was injected in two divided doses (2× 40 mg/kg, i.p. at 16 h apart). The animals were observed for motor functions 48 h after the first MPTP injection. The animals were then euthanized, the brains collected to analyze SYN pathology, cytokines, and oxidative stress levels in the substantia nigra region. The NGN significantly downregulated SYN and upregulated dopamine transporter (DAT) and tyrosine hydroxylase (TH) protein expressions. It also downregulated tumor necrosis factor-α (TNFα) and interleukin 1β (IL1β) mRNA expressions and improved superoxide dismutase levels. It also reduced glutathione levels when compared to vehicle-treated PD animals. The upregulation of TH corroborates to an increase in dopamine, DOPAC, and homovanillic acid turnover and motor functions with NGN treatment. To summarize, NGN, a dietary flavone, has the potential to counteract MPTP-induced dopaminergic degeneration by regulating SYN pathology, neuroinflammation, and oxidative stress. This warrants the investigation of NGN’s potential effects in a genetic model of PD.
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Abbreviations
- AEC:
-
3-amino-9-ethylcarbazole
- ANOVA:
-
Analysis of variance
- ATP:
-
Adenosine triphosphate
- BSA:
-
Bovine serum albumin
- CMC:
-
Carboxy methyl cellulose
- DAT:
-
Dopamine Transporter
- DOPAC:
-
3,4-dihydroxyphenylacetic acid
- GSH:
-
Reduced glutathione
- HVA:
-
Homovanillic acid
- i.p.:
-
Intraperitoneal
- IL-1β:
-
Interleukin 1 beta
- MPTP:
-
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- NGN:
-
Naringenin
- NO:
-
Nitric oxide
- PBS:
-
Phosphate-buffered saline
- PD:
-
Parkinson’s disease
- RNA:
-
Ribonucleic acid
- RT-PCR:
-
Reverse transcriptase-polymerase chain reaction
- SEM:
-
Standard error of the mean
- SNpc:
-
Substantia nigra
- SOD:
-
Superoxide dismutase
- SYN:
-
α-Synuclein
- TBS:
-
Tween phosphate-buffered saline
- TH:
-
Tyrosine hydroxylase
- TNF-α:
-
Tumor necrosis factor alpha
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SBC profusely thanks the Scientific and Engineering Research Board (SERB), Department of Science and Technology (DST), Govt of India, for awarding (NO:SB/FT/LS-293/2012) young scientist grant.
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Mani, S., Sekar, S., Barathidasan, R. et al. Naringenin Decreases α-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson’s Disease Model in Mice. Neurotox Res 33, 656–670 (2018). https://doi.org/10.1007/s12640-018-9869-3
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DOI: https://doi.org/10.1007/s12640-018-9869-3