Subcutaneous Rotenone Exposure Causes Highly Selective Dopaminergic Degeneration and α-Synuclein Aggregation

doi:10.1006/exnr.2002.8072

Experimental Neurology

Volume 179, Issue 1, January 2003, Pages 9-16

https://doi.org/10.1006/exnr.2002.8072 Get rights and content

Abstract

Previous studies demonstrated that chronic systemic exposure to the pesticide and mitochondrial toxin rotenone through jugular vein cannulation reproduced many features of Parkinson's disease (PD) in rats, including nigrostriatal dopaminergic degeneration and formation of α-synuclein-positive cytoplasmic inclusions in nigral neurons (R. Betarbet et al., 2000, Nat. Neurosci. 3, 1301–1306). Although novel and conceptually important, the rotenone model of PD suffered from being extremely labor-intensive. The current paper demonstrates that these same features of PD can be reproduced by chronic, systemic exposure to rotenone following implantation of subcutaneous osmotic pumps. Chronic subcutaneous exposure to low doses of rotenone (2.0–3.0 mg/kg/day) caused highly selective nigrostriatal dopaminergic lesions. Striatal neurons containing DARPP-32 (dopamine and cAMP-regulated phosphoprotein) remained intact with normal morphology, and NeuN staining revealed normal neuronal nuclear morphology. Neurons of the globus pallidus and subthalamic nucleus were spared. Subcutaneous rotenone exposure caused α-synuclein-positive cytoplasmic aggregates in nigral neurons. This new protocol for chronic rotenone administration is a substantial improvement in terms of simplicity and throughput.

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¹: These authors contributed equally to this work.

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Regular ArticleSubcutaneous Rotenone Exposure Causes Highly Selective Dopaminergic Degeneration and α-Synuclein Aggregation

Abstract

Behav. Brain Res.

Exp. Neurol.

J. Biol. Chem.

Biochim. Biophys. Acta

Brain Res.

Am. J. Pathol.

Eur. J. Pharmacol.

Neuroscience

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Exp. Neurol.

Lancet

Biochem. Biophys. Res. Commun.

Life Sci.

Neuroscience

Lancet

Exp. Neurol.

Brain Res.

J. Biol. Chem.

Exp. Neurol.

Brain Res.

FEBS Lett.

FEBS Lett.

A generalised increase in protein carbonyls in the brain in Parkinson's but not incidental Lewy body disease

J. Neurochem.

Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid

J. Neurosci.

Chronic systemic pesticide exposure reproduces features of Parkinson's disease

Nat. Neurosci.

Topological analysis of striatal lesions induced by 3-nitropropionic acid in the Lewis rat

NeuroReport

Mitochondrial respiratory chain activity in skeletal muscle from patients with Parkinson's disease

Neurology

Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct

Science

Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease

J. Neurochem.

Regular Article
Subcutaneous Rotenone Exposure Causes Highly Selective Dopaminergic Degeneration and α-Synuclein Aggregation