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Updated: Aug 17, 2026
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Glia cell number modulates sensitivity to MPTP in mice
Michelle Smeyne1, Yun Jiao, Kennie R Shepherd
1Department of Developmental Neurobiology, Saint Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Abstract:
Free radical damage has been shown to play a significant role in the pathogenesis of a number of neurodegenerative diseases including Parkinson's disease. One model of experimental parkinsonism is the loss of substantia nigra cells following administration of MPTP. Previously, it has been shown that a number of inbred strains of mice have differential responses to this toxin, and this difference is dependent on glial cells. In this study, the number of glial cells in the substantia nigra pars compacta of C57Bl/6J (MPTP-sensitive) and Swiss Webster (MPTP-resistant) strains of mice was examined. The C57Bl/6J mice have an approximately 50% lower number of GFAP+ and S-100beta glial cells than the Swiss Webster mice. C57Bl/6J mice have a 25% increased number of resident nonactivated microglial cells. To determine whether this difference in cell number has functional significance, we used an in vitro SN culture system that allowed us to manipulate the number of glial cells. When C57Bl/6 neurons were grown on a glial mat plated with twice the number of cells, we were able to rescue the MPTP-sensitive neurons from toxin-induced cell death. This suggests that the number of glial cells in the SNpc may be an important factor in the survival of dopaminergic neurons following exposure to xenobiotics.
Insights
Glial cell numbers influence MPTP toxin sensitivity in Parkinson's disease models. Increasing glial cells in MPTP-sensitive mice rescued dopaminergic neurons from damage, suggesting a protective role.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Free radical damage contributes to neurodegenerative diseases like Parkinson's.
- MPTP toxin induces experimental parkinsonism by causing substantia nigra cell loss.
- Inbred mouse strains exhibit differential MPTP sensitivity, influenced by glial cells.
Purpose of the Study:
- To investigate the role of glial cell numbers in MPTP-induced neurodegeneration.
- To compare glial cell populations in MPTP-sensitive (C57Bl/6J) and MPTP-resistant (Swiss Webster) mice.
- To determine if glial cell quantity affects dopaminergic neuron survival.
Main Methods:
- Quantified glial cells (GFAP+, S-100beta, microglia) in the substantia nigra pars compacta of C57Bl/6J and Swiss Webster mice.
- Utilized an in vitro substantia nigra culture system to manipulate glial cell numbers.
- Exposed C57Bl/6J neurons to MPTP toxin under varying glial cell densities.
Main Results:
- C57Bl/6J mice had 50% fewer GFAP+ and S-100beta glial cells than Swiss Webster mice.
- C57Bl/6J mice showed a 25% increase in nonactivated resident microglial cells.
- Increasing glial cell density in vitro rescued MPTP-sensitive neurons from toxin-induced death.
Conclusions:
- Glial cell number in the substantia nigra pars compacta is a critical factor in dopaminergic neuron survival against xenobiotics.
- Differential glial cell populations may explain varying MPTP sensitivity between mouse strains.
- Glial cell augmentation shows potential for neuroprotection in Parkinson's disease models.
