Naringenin Decreases α-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson’s Disease Model in Mice

Sugumar Mani, Sathiya Sekar, Rajamani Barathidasan, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Murugan Sevanan, Saravana Babu Chidambaram, Musthafa Mohamed Essa, Gilles J. Guillemin, Meena Kishore Sakharkar

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11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalNeurotoxicity Research
DOIs
Publication statusAccepted/In press - Feb 9 2018

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Keywords

  • Motor functions
  • MPTP
  • Naringenin
  • Neuroinflammation
  • Oxidative stress
  • Parkinson’s disease
  • α-Synuclein

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Mani, S., Sekar, S., Barathidasan, R., Manivasagam, T., Thenmozhi, A. J., Sevanan, M., ... Sakharkar, M. K. (Accepted/In press). Naringenin Decreases α-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson’s Disease Model in Mice. Neurotoxicity Research, 1-15. https://doi.org/10.1007/s12640-018-9869-3