MAP kinase superfamily in amyloid β-protein fragment 25-35-induced inflammation andapoptosis in rat hippocampus in vivo
- VernacularTitle:MAP激酶家族在淀粉样β蛋白片段25～35引起的大鼠海马炎症反应及细胞凋亡中的作用
- Author:
Ying JIN
;
Ying FAN
;
Enzhi YAN
;
Zhihong ZONG
;
Cuifen BAO
;
Zhi LI
- Publication Type:Journal Article
- Keywords:
amyloid beta-protein;
inflammation;
MAP kinase signaling system;
p38 MAP kinase;
caspases;
apoptosis
- From:
Chinese Journal of Pharmacology and Toxicology
2005;19(3):161-168
- CountryChina
- Language:Chinese
-
Abstract:
AIM To explore the mechanism of amyloid β-protein fragment 25-35(Aβ25-35)-induced inflammation and apoptosis in rat hippocampus in vivo by studying mitogen-activated protein kinase (MAPK) signaling pathway and the protective effect of anti-inflammatory drug ibuprofen. METHODS Rats were given ibuprofen (7.5 mg·kg-1 daily, ig) for 3 weeks prior to and 1 week after icv single dose of Aβ25-35 (10 μL, 1 mmol·L-1). Seven days after injection, Nissl staining and immunocytochemical technique were employed to determine the morphology of pyramidal neurons and astrocyte infiltration in hippocampal CA1. The expressions of IL-1β, extracellular signal-regulated kinase (ERK), p38 MAPK, PKC, and caspase-3 were determined by Western blot. Reverse transcription-PCR analysis showed changes in IL-1β mRNA level. RESULTS Intracerebroventricular injection of Aβ25-35 elicited astrocyte activation and infiltration and caused a strong inflammatory reaction characterized by increased IL-1β production and elevated IL-1β mRNA level. The inflammatory reaction was accompanied by the loss of pyramidal neurons in hippocampal CA1. The phosphorylation of p38 MAPK was significantly increased, on the other hand, the phosphorylation of ERK was significantly reduced and these were coupled with the increase of caspase-3 expression in hippocampal CA1. Ibuprofen (7.5 mg·kg-1 daily, 4 weeks) significantly reduced Aβ-induced IL-1β expression, caspase-3 expression and p38 MAPK activation. The loss of pyramidal neurons was also significantly attenuated by treatment with ibuprofen. CONCLUSION The activation of p38 MAPK and the down-regulation of ERK play a pivotal role in the inflam-matory response and apoptosis evoked by Aβ25-35 in vivo, which can be prevented by ibuprofen.
