Lowering ambient or core body temperature elevates striatal MPP + levels and enhances toxicity to dopamine neurons in MPTP-treated mice

Lily Y. Moy, David S. Albers

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The neuroprotective effects of lowering body temperature have been well documented in various models of neuronal injury. The present study investigated the effects a lower ambient or core body temperature would have on damage to striatal dopamine (DA) neurons produced by 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP). Mice received systemic MPTP treatment at two different temperatures, 4°C and 22°C. MPTP-treated mice maintained at 4°C demonstrated (1) a greater hypothermic response, (2) a significant reduction in striatal DA content and tyrosine hydroxylase (TH) activity, and (3) significantly greater striatal 1-methyl-4-phenylpyridinium (MPP +) levels, as compared to mice dosed with MPTP at room temperature. Parallel studies with methamphetamine (METH) were conducted since temperature appears to play a pivotal role in the mediation of damage to DA neurons by this CNS stimulant in rodents. As previously reported, METH-induced hyperthermia and the subsequent loss of striatal DA content were attenuated in animals dosed at 4°C. We also evaluated the effects a hypothermic state induced by pharmacological agents would have on striatal neurochemistry and MPP + levels following MPTP treatment. Concurrent administration of MK-801 or 8-OHDPAT increased the striatal MPP + levels following MPTP treatment. However, only 8-OHDPAT potentiated the MPTP-induced decrements of striatal DA content and TH activity; MK-801 did not affect MPTP decreases in these striatal markers of dopaminergic damage. Altogether, these findings indicate that temperature has a profound effect on striatal MPP + levels and MPTP-induced damage to DA neurons in mice.

Original languageEnglish (US)
Pages (from-to)264-269
Number of pages6
JournalBrain research
Volume790
Issue number1-2
DOIs
StatePublished - Apr 20 1998

Fingerprint

Corpus Striatum
Dopaminergic Neurons
Body Temperature
8-Hydroxy-2-(di-n-propylamino)tetralin
Dopamine
Temperature
Dizocilpine Maleate
Methamphetamine
Tyrosine 3-Monooxygenase
1-Methyl-4-phenylpyridinium
Neurochemistry
4-phenyl-1,2,3,6-tetrahydropyridine
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Induced Hyperthermia
Neuroprotective Agents
Rodentia
Therapeutics
Pharmacology

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Molecular Biology
  • Neuroscience(all)
  • Developmental Biology

Keywords

  • Core temperature
  • Dopamine
  • MPTP
  • Methamphetamine
  • Mice
  • Neurotoxicity
  • Striatum

Cite this

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title = "Lowering ambient or core body temperature elevates striatal MPP + levels and enhances toxicity to dopamine neurons in MPTP-treated mice",
abstract = "The neuroprotective effects of lowering body temperature have been well documented in various models of neuronal injury. The present study investigated the effects a lower ambient or core body temperature would have on damage to striatal dopamine (DA) neurons produced by 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP). Mice received systemic MPTP treatment at two different temperatures, 4°C and 22°C. MPTP-treated mice maintained at 4°C demonstrated (1) a greater hypothermic response, (2) a significant reduction in striatal DA content and tyrosine hydroxylase (TH) activity, and (3) significantly greater striatal 1-methyl-4-phenylpyridinium (MPP +) levels, as compared to mice dosed with MPTP at room temperature. Parallel studies with methamphetamine (METH) were conducted since temperature appears to play a pivotal role in the mediation of damage to DA neurons by this CNS stimulant in rodents. As previously reported, METH-induced hyperthermia and the subsequent loss of striatal DA content were attenuated in animals dosed at 4°C. We also evaluated the effects a hypothermic state induced by pharmacological agents would have on striatal neurochemistry and MPP + levels following MPTP treatment. Concurrent administration of MK-801 or 8-OHDPAT increased the striatal MPP + levels following MPTP treatment. However, only 8-OHDPAT potentiated the MPTP-induced decrements of striatal DA content and TH activity; MK-801 did not affect MPTP decreases in these striatal markers of dopaminergic damage. Altogether, these findings indicate that temperature has a profound effect on striatal MPP + levels and MPTP-induced damage to DA neurons in mice.",
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Lowering ambient or core body temperature elevates striatal MPP + levels and enhances toxicity to dopamine neurons in MPTP-treated mice. / Moy, Lily Y.; Albers, David S.

In: Brain research, Vol. 790, No. 1-2, 20.04.1998, p. 264-269.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lowering ambient or core body temperature elevates striatal MPP + levels and enhances toxicity to dopamine neurons in MPTP-treated mice

AU - Moy, Lily Y.

AU - Albers, David S.

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