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Olfactory Assays for Mouse Models of Neurodegenerative Disease
Published on: August 25, 2014
Osteopetrotic (op/op) mice have reduced microglia, no Abeta deposition, and no changes in dopaminergic neurons
Yoichi Kondo1, Cynthia A Lemere, Timothy J Seabrook
1Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA. kondoy@svm.vetmed.wisc.edu
Background:
Activation of microglia is a part of the inflammatory response in neurodegenerative diseases but its role in the pathophysiology of these diseases is still unclear. The osteopetrotic (op/op) mouse lacks colony-stimulating factor-1 (CSF-1) and thus has a deficiency in microglia and macrophages. Prior reports have demonstrated that op/op mice deposit amyloid beta (Abeta) plaques, similar to those found in Alzheimer's disease. The purpose of these studies was to confirm this and to determine if the lack of CSF-1 affects the development of dopaminergic neurons and the expression of CD200, a known microglial inhibitory protein.
Method:
We examined the central nervous system of op/op mice at 30 days, 60 days and 7 months of age and wildtype littermates at 30 days using immunohistochemistry and histochemistry.
Results:
We found a decrease in the number of microglia in 1 month-old op/op mice compared to wildtype (WT) littermates as measured by CD11b, CD45, CD32/16, CD68, CD204 and F4/80 immunoreactivity. Abeta plaques were not detected, while the number of dopaminergic neurons appeared normal. The expression of CD200 appeared to be normal, but there appeared to be a lower expression in the substantia nigra.
Conclusion:
In contrast to a prior report we did not detect Abeta deposition in the central nervous system of op/op mice at 30 days, 60 days or 7 months of age and there was a normal number of dopaminergic neurons. This indicates that op/op mice may be useful to examine the effects of microglia on neurodegenerative disease progression by breeding them to different transgenic mouse models. In addition, the lack of CSF-1 does not appear to affect CD200 expression by neurons but we did note a decrease in the substantia nigra of op/op and WT mice, suggesting that this may be a mechanism by which microglia control may be attenuated in this specific area during Parkinson's disease.
Insights
Osteopetrotic (op/op) mice, lacking colony-stimulating factor-1 (CSF-1), show reduced microglia but no amyloid-beta plaques or altered dopaminergic neurons. These mice may model neuroinflammation in Parkinson's disease research.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglial activation is key in neuroinflammation, but its precise role in neurodegenerative diseases remains unclear.
- Osteopetrotic (op/op) mice, deficient in colony-stimulating factor-1 (CSF-1), have reduced microglia and macrophages.
- Previous studies indicated op/op mice develop amyloid-beta plaques, characteristic of Alzheimer's disease.
Purpose of the Study:
- To verify amyloid-beta plaque deposition in op/op mice.
- To investigate the impact of CSF-1 deficiency on dopaminergic neuron development.
- To assess changes in CD200 expression, a microglial inhibitory protein, in op/op mice.
Main Methods:
- Central nervous systems of op/op mice and wildtype littermates were analyzed at various ages (30 days, 60 days, 7 months).
- Immunohistochemistry and histochemistry techniques were employed to examine cellular markers and protein expression.
- Specific markers assessed included CD11b, CD45, CD32/16, CD68, CD204, F4/80, and CD200.
Main Results:
- A significant decrease in microglia was observed in 1-month-old op/op mice compared to wildtype controls.
- Amyloid-beta plaques were not detected in the central nervous system of op/op mice at any age studied.
- Dopaminergic neuron counts were normal, and CD200 expression was generally unaffected, though reduced in the substantia nigra.
Conclusions:
- Contrary to prior reports, op/op mice do not exhibit amyloid-beta deposition and maintain normal dopaminergic neuron numbers.
- Op/op mice serve as a valuable model for studying microglial roles in neurodegenerative diseases when crossed with transgenic models.
- CSF-1 deficiency does not impair neuronal CD200 expression; reduced substantia nigra CD200 in op/op and wildtype mice suggests a potential mechanism for microglial dysregulation in Parkinson's disease.
