TY - JOUR
T1 - Naringenin Decreases α-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson’s Disease Model in Mice
AU - Mani, Sugumar
AU - Sekar, Sathiya
AU - Barathidasan, Rajamani
AU - Manivasagam, Thamilarasan
AU - Thenmozhi, Arokiasamy Justin
AU - Sevanan, Murugan
AU - Chidambaram, Saravana Babu
AU - Essa, Musthafa Mohamed
AU - Guillemin, Gilles J.
AU - Sakharkar, Meena Kishore
N1 - Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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.
KW - MPTP
KW - Motor functions
KW - Naringenin
KW - Neuroinflammation
KW - Oxidative stress
KW - Parkinson’s disease
KW - α-Synuclein
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U2 - 10.1007/s12640-018-9869-3
DO - 10.1007/s12640-018-9869-3
M3 - Article
C2 - 29427283
AN - SCOPUS:85041848100
SN - 1029-8428
VL - 33
SP - 656
EP - 670
JO - Neurotoxicity Research
JF - Neurotoxicity Research
IS - 3
ER -