Kondo Yoichi, Lemere Cynthia A, Seabrook Timothy J
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
J Neuroinflammation. 2007 Dec 20;4:31. doi: 10.1186/1742-2094-4-31.
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.
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.
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.
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.
小胶质细胞的激活是神经退行性疾病炎症反应的一部分，但其在这些疾病病理生理学中的作用仍不清楚。骨硬化症（op/op）小鼠缺乏集落刺激因子-1（CSF-1），因此小胶质细胞和巨噬细胞数量不足。先前的报道表明，op/op小鼠会沉积β-淀粉样蛋白（Aβ）斑块，类似于在阿尔茨海默病中发现的斑块。这些研究的目的是证实这一点，并确定CSF-1的缺乏是否会影响多巴胺能神经元的发育以及CD200（一种已知的小胶质细胞抑制蛋白）的表达。
我们使用免疫组织化学和组织化学方法，在30天、60天和7个月龄时检查op/op小鼠的中枢神经系统，并在30天时检查野生型同窝小鼠的中枢神经系统。
通过CD11b、CD45、CD32/16、CD68、CD204和F4/80免疫反应性检测发现，与野生型（WT）同窝小鼠相比，1月龄op/op小鼠的小胶质细胞数量减少。未检测到Aβ斑块，而多巴胺能神经元数量似乎正常。CD200的表达似乎正常，但黑质中的表达似乎较低。
与先前的报道相反，我们在30天、6天或7个月龄的op/op小鼠中枢神经系统中未检测到Aβ沉积且多巴胺能神经元数量正常。这表明通过将op/op小鼠与不同的转基因小鼠模型杂交，op/op小鼠可能有助于研究小胶质细胞对神经退行性疾病进展的影响。此外，CSF-1的缺乏似乎不影响神经元的CD200表达，但我们确实注意到op/op和WT小鼠黑质中的表达减少，这表明这可能是帕金森病期间该特定区域小胶质细胞控制减弱的一种机制。
