Expression And Distribution Of MKP-1, Negative Regulatory Factor Of MAPK, In The Brain Of APP/PS1 Double Transgenic Mice

Objective:To investigate the expression and distribution of MKP-1 in the brain of APP/PS 1 double transgenic mice and their wildtype cousins, and to observe the expression of MKP-1 in the different age of APP/PS1 double transgenic mice so as to clerify the relationship bewteen MKP-1 and Alzheimer’s sisease.Methods:3-month old mice,8-month old mice and 12-month old mice were selected, and immunohistochemical staining (IHC) was used to detect the expression and distribution of MKP-1 in the brain of APP/PS1 double transgenic mice and their wildtype cousins. The pathological changes of MKP-1 was examined by immunoflurescence,Western blot (WB) was employed to test the levels of MKP-1, brain derived neurotrophic factor (BDNF), extracellular signal-regulated kinases (ERK), p-ERK, c-JUN N-terminal kinases (JNK), p-JNK and p38 kinases(p38) and Real Time-PCR was used to detect the levels of MKP-1 mRNA and BDNF mRNA. The co-expression of MKP-1 and 4G8, p-ERK and 4G8, p-JNK and 4G8, p-p38 and 4G8 were observed by immunofluorescent staining.Results:1. Morphological test:MKP-1 scatters widely in the brain of APP/PS1 double transgenic mice, including cerebral cortex, hippocampus, corpus striatum, olfactory bulb and cerebellum. Expression of MKP-1 was significangtly lower in the brain of APP/PS1 double transgenic mice than that in their wildtypesp (P<0.05), whose expression was decreased with the increased of age (P<0.05). Meanwhile, MKP-1 was found that it could co-express with a part of Senile plaques (SPs). The mount of SP that MKP-1 could express was increased with age.2. Western blot tests:With the increased of APP/PS1 double transgenic mice age, protein expression of MKP-1 (p<0.05) and BDNF (p<0.05) were gradually decreased, while protein expression of p-JNK(p<0.05), p-ERK (p<0.05) and p-P38 (p<0.05) were gradually increased, and the protein expression of JNK, ERK and P38 were never changed all the time.Conclusion:The expreesion of MKP-1 are different in the brain of APP/PS1 double transgenic mice and in their wildtypes. A part of SPs can be expressed by MKP-1, which suggests that MKP-1 have the relationship with the produce of Aβ and the pathogenesis of AD.