Salicylate protects against MPTP-induced impairments in dopaminergic neurotransmission at the striatal and nigral level in mice

B Ferger, Peter Teismann, C D Earl, K Kuschinsky, W H Oertel

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The analgesic and anti-inflammatory drug sodium salicylate was studied for its potential protective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. C 57BL/6 mice were treated with a single dose of sodium salicylate (50 mg/kg or 100 mg/kg i.p.) or saline immediately before injection of MPTP (30 mg/kg or 40 mg/kg s.c.) or saline. Analysis of striatal dopamine and metabolites as well as immunostaining for tyrosine hydroxylase of nigral sections was performed 7 days after MPTP treatment. MPTP (30 mg/kg) led to a strong decrease in striatal dopamine levels (1.87+/-0.27 ng/mg) compared to saline-treated controls (15.72+/-0.78 ng/mg), which was significantly attenuated by sodium salicylate 50 mg/kg and 100 mg/kg (5.59+/-0.56 ng/mg and 8.64+/-0.89 ng/mg, respectively). Remarkably, the MPTP-induced loss of tyrosine hydroxylase immunoreactivity in nigral cell bodies was nearly completely prevented by the higher dose of sodium salicylate. Furthermore, salicylate demonstrated radical scavenging effects in an in vitro Fenton system indicated by HPLC determination of the dihydroxylated reaction products of salicylate, namely, 2,3- and 2,5-dihydroxybenzoic acid. The protective effects of salicylate against reversible or irreversible impairments in dopaminergic neurotransmission after MPTP treatment may be related to its radical scavenging properties and other mechanisms which need to be clarified.
Original languageEnglish
Pages (from-to)256-261
Number of pages6
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume360
Issue number3
DOIs
Publication statusPublished - 1 Sep 1999

Fingerprint

Corpus Striatum
Salicylates
Sodium Salicylate
Substantia Nigra
Synaptic Transmission
Tyrosine 3-Monooxygenase
Dopamine
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Non-Steroidal Anti-Inflammatory Agents
Parkinson Disease
High Pressure Liquid Chromatography
4-phenyl-1,2,3,6-tetrahydropyridine
Injections
Therapeutics
Pharmaceutical Preparations

Keywords

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 3,4-Dihydroxyphenylacetic Acid
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cell Count
  • Disease Models, Animal
  • Dopamine
  • Dopamine Agents
  • Dose-Response Relationship, Drug
  • Free Radical Scavengers
  • Homovanillic Acid
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neostriatum
  • Neurons
  • Parkinson Disease, Secondary
  • Protective Agents
  • Salicylates
  • Substantia Nigra
  • Synaptic Transmission
  • Tyrosine 3-Monooxygenase
  • Salicylic acid
  • Hydroxyl radicals
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Parkinson’s disease
  • Radical scavenger
  • Neuroprotection

Cite this

Salicylate protects against MPTP-induced impairments in dopaminergic neurotransmission at the striatal and nigral level in mice. / Ferger, B; Teismann, Peter; Earl, C D; Kuschinsky, K; Oertel, W H.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 360, No. 3, 01.09.1999, p. 256-261.

Research output: Contribution to journalArticle

Ferger, B ; Teismann, Peter ; Earl, C D ; Kuschinsky, K ; Oertel, W H. / Salicylate protects against MPTP-induced impairments in dopaminergic neurotransmission at the striatal and nigral level in mice. In: Naunyn-Schmiedeberg's Archives of Pharmacology. 1999 ; Vol. 360, No. 3. pp. 256-261.
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AB - The analgesic and anti-inflammatory drug sodium salicylate was studied for its potential protective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. C 57BL/6 mice were treated with a single dose of sodium salicylate (50 mg/kg or 100 mg/kg i.p.) or saline immediately before injection of MPTP (30 mg/kg or 40 mg/kg s.c.) or saline. Analysis of striatal dopamine and metabolites as well as immunostaining for tyrosine hydroxylase of nigral sections was performed 7 days after MPTP treatment. MPTP (30 mg/kg) led to a strong decrease in striatal dopamine levels (1.87+/-0.27 ng/mg) compared to saline-treated controls (15.72+/-0.78 ng/mg), which was significantly attenuated by sodium salicylate 50 mg/kg and 100 mg/kg (5.59+/-0.56 ng/mg and 8.64+/-0.89 ng/mg, respectively). Remarkably, the MPTP-induced loss of tyrosine hydroxylase immunoreactivity in nigral cell bodies was nearly completely prevented by the higher dose of sodium salicylate. Furthermore, salicylate demonstrated radical scavenging effects in an in vitro Fenton system indicated by HPLC determination of the dihydroxylated reaction products of salicylate, namely, 2,3- and 2,5-dihydroxybenzoic acid. The protective effects of salicylate against reversible or irreversible impairments in dopaminergic neurotransmission after MPTP treatment may be related to its radical scavenging properties and other mechanisms which need to be clarified.

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KW - Salicylic acid

KW - Hydroxyl radicals

KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

KW - Parkinson’s disease

KW - Radical scavenger

KW - Neuroprotection

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M3 - Article

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JO - Naunyn-Schmiedeberg's Archives of Pharmacology

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