Premium
P1‐325: Apolipoprotein E‐isoform dependent hippocampal neurodegeneration to kainic acid‐induced excitotoxicity
Author(s) -
Zhang Xing-Mei,
Mao Xi-Jing,
Zhang Hong-Liang,
Pham Therese,
Adem Abdu,
Winblad Bengt,
Zhu Jie
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.878
Subject(s) - kainic acid , neurodegeneration , microglia , medicine , hippocampal formation , endocrinology , biology , pharmacology , inflammation , receptor , glutamate receptor , disease
Background: The diverse effects of apolipoprotein E (apoE) isoforms in the neurodegenerative disorders have been evidenced. In addition to its physiological role in cholesterol transport, apoE has an intricate biological function in modulating immune responses. In the present study, we aimed to investigate the individual roles of apoE isoforms in the kainic acid (KA)-induced hippocampal neurodegeneration with consideration the immune responses. Methods: ApoE2, apoE3 and apoE4 transgenic mice as well as wild-type male mice (7-weeks-old) were treated with KA (40mg/kg bodyweight) intranasally. The KA-induced seizure activity and pathological changes were recorded. Additionally, before and after KA administration, all groups of mice were performed a series of behavioral tests, including elevated plus-maze, open-field test, novel objects exploration test and the spontaneous alteration behavior in a Y-maze. Microglia activation and astrocyte proliferation were evaluated by immunohistochemistry. The inflammatory molecules secreted by microglia such as MHC-II, CD86, F4/80, CD95, inducible nitric oxide synthase (iNOS), TNF-a, IL-6, IL-12 and IL-17 were detected by flow cytometry. Results: We found that the same amount of KA induced severer seizure activity and pathological changes in apoE4 transgenic mice compared to other groups of mice. In open-field test, KA-treated apoE4 mice showed lower locomotion and rearing activity than KA-treated other groups of mice. In elevated plus-maze test, KA administration resulted in higher counts of head drops in the cross-area in apoE4 transgenic mice, indicating the changed risk assessment. Detected by flow cytometry, microglia-secreted CD86 and MHCII elevated in KA-treated apoE4 transgenic mice. Additionally, there was also an apoE-isoform dependent elevation of iNOS expression 1 day after KA insult. Conclusions: In conclusion, overexpression of apoE4 deteriorated KA-induced hippocampal neurodegeneration, which might be resulted from the up-regulated microglia activation and followed more secretion of the inflammatory molecules.