Source Paper
Parkinson-like syndrome induced by continuous MPTP infusion: Convergent roles of the ubiquitin-proteasome system and α-synuclein
Francesco Fornai, Oliver M. Schlüter, Paola Lenzi, Marco Gesi, Riccardo Ruffoli et al.
Proceedings of the National Academy of Sciences • 2005
Sporadic MPTP Injection
Objective: To compare acute dopaminergic damage from sporadic MPTP injections with continuous MPTP administration effects, and to evaluate the role of α-synuclein in MPTP-induced Parkinson-like syndrome
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Equipment1
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Materials1
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Protocol Steps
Sporadic MPTP injection protocol
Administer sporadic injections of MPTP to mice
Note: This is the comparison condition to continuous administration
View evidence from paper
“sporadic injections of the mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)”
Continuous MPTP administration
Deliver MPTP continuously using an osmotic minipump
Note: Continuous low-level exposure protocol
View evidence from paper
“continuous MPTP administration with an osmotic minipump and mimics many features of the human disease”
Behavioral assessment
Monitor and record progressive behavioral changes in treated mice
Note: Only continuous MPTP administration produced progressive behavioral changes
View evidence from paper
“only continuous administration of MPTP produced progressive behavioral changes”
Neurological examination
Assess nigral cell loss and striatal dopamine depletion
Note: Both sporadic and continuous MPTP led to severe striatal dopamine depletion and nigral cell loss
View evidence from paper
“both sporadic and continuous MPTP administration led to severe striatal dopamine depletion and nigral cell loss”
Inclusion body assessment
Examine nigral inclusions immunoreactive for ubiquitin and α-synuclein
Note: Only continuous MPTP triggered formation of nigral inclusions
View evidence from paper
“only continuous administration of MPTP produced progressive behavioral changes and triggered formation of nigral inclusions immunoreactive for ubiquitin and α-synuclein”
Metabolic assessment
Measure glucose uptake and ubiquitin-proteasome system function
Note: Only continuous MPTP infusions caused long-lasting activation of glucose uptake and inhibition of ubiquitin-proteasome system
View evidence from paper
“only continuous MPTP infusions caused long-lasting activation of glucose uptake and inhibition of the ubiquitin-proteasome system”
α-synuclein knockout comparison
Repeat continuous MPTP administration in mice lacking α-synuclein and compare outcomes
Note: In α-synuclein knockout mice, continuous MPTP induced metabolic activation but behavioral symptoms and neuronal cell death were almost completely alleviated
View evidence from paper
“In mice lacking α-synuclein, continuous MPTP delivery still induced metabolic activation, but induction of behavioral symptoms and neuronal cell death were almost completely alleviated”