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

Research output: Contribution to journalArticle

9 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

Fingerprint

Synucleins
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Parkinson Disease
Pathology
Animals
flavone
Oxidative stress
Tyrosine 3-Monooxygenase
Oxidative Stress
Down-Regulation
Citrus fruits
3,4-Dihydroxyphenylacetic Acid
Homovanillic Acid
Dopamine Plasma Membrane Transport Proteins
Citrus
Genetic Models
Substantia Nigra
Interleukin-1
Inbred C57BL Mouse
Superoxide Dismutase

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

Naringenin Decreases α-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson’s Disease Model in Mice. / Mani, Sugumar; Sekar, Sathiya; Barathidasan, Rajamani; Manivasagam, Thamilarasan; Thenmozhi, Arokiasamy Justin; Sevanan, Murugan; Chidambaram, Saravana Babu; Essa, Musthafa Mohamed; Guillemin, Gilles J.; Sakharkar, Meena Kishore.

In: Neurotoxicity Research, 09.02.2018, p. 1-15.

Research output: Contribution to journalArticle

Mani, S, Sekar, S, Barathidasan, R, Manivasagam, T, Thenmozhi, AJ, Sevanan, M, Chidambaram, SB, Essa, MM, Guillemin, GJ & Sakharkar, MK 2018, 'Naringenin Decreases α-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson’s Disease Model in Mice', Neurotoxicity Research, pp. 1-15. https://doi.org/10.1007/s12640-018-9869-3
Mani, Sugumar ; Sekar, Sathiya ; Barathidasan, Rajamani ; Manivasagam, Thamilarasan ; Thenmozhi, Arokiasamy Justin ; Sevanan, Murugan ; Chidambaram, Saravana Babu ; Essa, Musthafa Mohamed ; Guillemin, Gilles J. ; Sakharkar, Meena Kishore. / Naringenin Decreases α-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson’s Disease Model in Mice. In: Neurotoxicity Research. 2018 ; pp. 1-15.
@article{ecde982468434d8594bf9a637d60a293,
title = "Naringenin Decreases α-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson’s Disease Model in Mice",
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.",
keywords = "Motor functions, MPTP, Naringenin, Neuroinflammation, Oxidative stress, Parkinson’s disease, α-Synuclein",
author = "Sugumar Mani and Sathiya Sekar and Rajamani Barathidasan and Thamilarasan Manivasagam and Thenmozhi, {Arokiasamy Justin} and Murugan Sevanan and Chidambaram, {Saravana Babu} and Essa, {Musthafa Mohamed} and Guillemin, {Gilles J.} and Sakharkar, {Meena Kishore}",
year = "2018",
month = "2",
day = "9",
doi = "10.1007/s12640-018-9869-3",
language = "English",
pages = "1--15",
journal = "Neurotoxicity Research",
issn = "1029-8428",
publisher = "Springer New York",

}

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

PY - 2018/2/9

Y1 - 2018/2/9

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 - Motor functions

KW - MPTP

KW - Naringenin

KW - Neuroinflammation

KW - Oxidative stress

KW - Parkinson’s disease

KW - α-Synuclein

UR - http://www.scopus.com/inward/record.url?scp=85041848100&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041848100&partnerID=8YFLogxK

U2 - 10.1007/s12640-018-9869-3

DO - 10.1007/s12640-018-9869-3

M3 - Article

AN - SCOPUS:85041848100

SP - 1

EP - 15

JO - Neurotoxicity Research

JF - Neurotoxicity Research

SN - 1029-8428

ER -