MPTP Mouse Model

 
The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxin leads to selective loss of dopaminergic (DA) neurons in the subatantia nigra pars compacta (SNpc) and loss of striatal projections of those neurons. Loss of the DA neurons in the SNpc and motor dysfunction mimic the clinical condition in Parkinson’s disease.
 
 

Neuronal loss in the substantia nigra pars compacta: A) TH-positive neurons in substantia nigra pars compacta (SNpc), bar=500 um B) Estimation of total number of TH-positive neurons in SNpc after acute MPTP exposure using stereology shows ca. 50% loss in MPTP vs. sham group. Data presented as mean of n=4, with S.E.M., Student t-test, ***p<0.001.

 
 
 

Denervation of striatum: A) TH-positive axons in striatum after saline and MPTP administration. B) Retrograde neurodegeneration after the MPTP injections leads to ca. 36% loss of TH-stained fibers in striatum. Data presented as mean of n=4, with S.E.M., Student t-test, **p<0.01.

 
 
 

Microglia activation: The death of dopaminergic neurons evoked by the MPTP injections leads to seven time increase in the area covered by microglia (visualized by Iba-1 staining) in the substantia nigra pars compacta region. Data presented as mean of n=4, with S.E.M., Student t-test, ***p<0.001.

 
 
 

Astrocyte activation: The death of dopaminergic neurons evoked by the MPTP injections leads to four time increase in the area covered by activated astrocytes (visualized by GFAP staining) in the substantia nigra pars compacta region. Data presented as mean of n=4, with S.E.M., Student t-test, **p<0.01.

 
 
Experimental End Points for Toxin Models

  • Behavior Testing
  • Quantification of DA neurons
  • Quantification of DA terminals
  • Quantification of inflammatory markers
  • 3D-EM evaluation of mitochondrial and synaptic changes