Digoxin prevents MPTP-induced dopamine depletion in mouse striatum

Steven Johnson, Stephen T. Gancher, William Woodward

Research output: Contribution to journalArticle

Abstract

Inhibition of Na+/K+ ATPase by cardiac glycosides has been shown to potentiate toxic effects of excitatory amino acids and mitochondrial poisons in neurons in vitro. The present study tested the hypothesis that the systemic administration of the cardiac glycoside, digoxin, potentiates effects of the dopamine neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) in vivo. Mice were injected with digoxin (1 mg/kg) or vehicle followed by MPTP (20 mg/kg) or saline 1 h later. After 1 or 8 days, mice were euthanized and dopamine levels in the striatum were measured by high-performance liquid chromatography with electrochemical detection. MPTP caused a significant 35-45% reduction in striatal dopamine levels compared to those in control mice. However, pretreatment with digoxin completely prevented the MPTP-induced dopamine depletion. This result was unexpected and suggests that cardiac glycosides may protect against MPTP neurotoxicity.

Original languageEnglish (US)
Pages (from-to)413-415
Number of pages3
JournalNeurotoxicology and Teratology
Volume19
Issue number5
DOIs
StatePublished - Sep 1997

Fingerprint

Digoxin
Cardiac Glycosides
Dopamine
Poisons
Corpus Striatum
Excitatory Amino Acids
Neurotoxins
High performance liquid chromatography
Neurons
Adenosine Triphosphatases
High Pressure Liquid Chromatography

Keywords

  • Cardiac glycoside
  • Na/K
  • Neuroprotection
  • Neurotoxicity
  • Sodium pump

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Toxicology

Cite this

Digoxin prevents MPTP-induced dopamine depletion in mouse striatum. / Johnson, Steven; Gancher, Stephen T.; Woodward, William.

In: Neurotoxicology and Teratology, Vol. 19, No. 5, 09.1997, p. 413-415.

Research output: Contribution to journalArticle

@article{ba7410914b55460d84f4b2237c91b2db,
title = "Digoxin prevents MPTP-induced dopamine depletion in mouse striatum",
abstract = "Inhibition of Na+/K+ ATPase by cardiac glycosides has been shown to potentiate toxic effects of excitatory amino acids and mitochondrial poisons in neurons in vitro. The present study tested the hypothesis that the systemic administration of the cardiac glycoside, digoxin, potentiates effects of the dopamine neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) in vivo. Mice were injected with digoxin (1 mg/kg) or vehicle followed by MPTP (20 mg/kg) or saline 1 h later. After 1 or 8 days, mice were euthanized and dopamine levels in the striatum were measured by high-performance liquid chromatography with electrochemical detection. MPTP caused a significant 35-45{\%} reduction in striatal dopamine levels compared to those in control mice. However, pretreatment with digoxin completely prevented the MPTP-induced dopamine depletion. This result was unexpected and suggests that cardiac glycosides may protect against MPTP neurotoxicity.",
keywords = "Cardiac glycoside, Na/K, Neuroprotection, Neurotoxicity, Sodium pump",
author = "Steven Johnson and Gancher, {Stephen T.} and William Woodward",
year = "1997",
month = "9",
doi = "10.1016/S0892-0362(97)00065-2",
language = "English (US)",
volume = "19",
pages = "413--415",
journal = "Neurotoxicology and Teratology",
issn = "0892-0362",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Digoxin prevents MPTP-induced dopamine depletion in mouse striatum

AU - Johnson, Steven

AU - Gancher, Stephen T.

AU - Woodward, William

PY - 1997/9

Y1 - 1997/9

N2 - Inhibition of Na+/K+ ATPase by cardiac glycosides has been shown to potentiate toxic effects of excitatory amino acids and mitochondrial poisons in neurons in vitro. The present study tested the hypothesis that the systemic administration of the cardiac glycoside, digoxin, potentiates effects of the dopamine neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) in vivo. Mice were injected with digoxin (1 mg/kg) or vehicle followed by MPTP (20 mg/kg) or saline 1 h later. After 1 or 8 days, mice were euthanized and dopamine levels in the striatum were measured by high-performance liquid chromatography with electrochemical detection. MPTP caused a significant 35-45% reduction in striatal dopamine levels compared to those in control mice. However, pretreatment with digoxin completely prevented the MPTP-induced dopamine depletion. This result was unexpected and suggests that cardiac glycosides may protect against MPTP neurotoxicity.

AB - Inhibition of Na+/K+ ATPase by cardiac glycosides has been shown to potentiate toxic effects of excitatory amino acids and mitochondrial poisons in neurons in vitro. The present study tested the hypothesis that the systemic administration of the cardiac glycoside, digoxin, potentiates effects of the dopamine neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) in vivo. Mice were injected with digoxin (1 mg/kg) or vehicle followed by MPTP (20 mg/kg) or saline 1 h later. After 1 or 8 days, mice were euthanized and dopamine levels in the striatum were measured by high-performance liquid chromatography with electrochemical detection. MPTP caused a significant 35-45% reduction in striatal dopamine levels compared to those in control mice. However, pretreatment with digoxin completely prevented the MPTP-induced dopamine depletion. This result was unexpected and suggests that cardiac glycosides may protect against MPTP neurotoxicity.

KW - Cardiac glycoside

KW - Na/K

KW - Neuroprotection

KW - Neurotoxicity

KW - Sodium pump

UR - http://www.scopus.com/inward/record.url?scp=0030824141&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030824141&partnerID=8YFLogxK

U2 - 10.1016/S0892-0362(97)00065-2

DO - 10.1016/S0892-0362(97)00065-2

M3 - Article

VL - 19

SP - 413

EP - 415

JO - Neurotoxicology and Teratology

JF - Neurotoxicology and Teratology

SN - 0892-0362

IS - 5

ER -