Distribution and expression of MKP-1 in the brain of APP/PS1 double-transgenic mice / 解放军医学杂志

ABSTRACT

Objective To study the distribution and expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) in the brain of APP/PS1 double-transgenic mice for clarifying the relationship between MKP-1 and Alzheimer’s disease (AD). Methods Three, eight and twelve month-old APP/PS1 double-transgenic mice (AD mice) were selected for this study (n=5), and the littermate wild-type male mice were used as normal control (n=5). The distribution and expression of MKP-1 in the brain of mice were assessed by immunohistochemical staining and Western blotting. Results Immunohistochemical staining revealed that MKP-1 was widely expressed in the brain of mice, including the cerebral cortex, hippocampus, and hypothalamus. The number of MKP-1-positive neurons in brains of 3 month-old AD mice (8824 ± 1397) was significant higher than that of 8 month-old mice (5278 ± 1764, P=0.008), and the number of MKP-1-positive neurons in brains of 8 month-old AD mice was significant higher than that of 12 month-old mice (2864 ± 1464, P=0.046). The result of Western blotting was consistent with the result of immunohistochemical staining (F=18.052, P=0.003). Compared with 8 month-old AD mice, the number of MKP-1-positive neurons in brain of littermate wild-type mice (10 121 ± 3657) was higher significantly (P=0.028). MKP-1-positive senile plaques were found in the brains of 8 month-old AD mice, but the number (6.00 ± 4.06) was significant lower than that of 4G8-positive senile plaques (25.60 ± 5.86, P=0.000). Immunofluorescence confocal microscopy revealed the presence of partial co-expression of MKP-1-positive substance and 4G8-positive senile plaques. Conclusion The expression of MKP-1 in the brain of AD mice is down-regulated with age, which may be related to the formation of senile plaques and occurrence of AD.