IL-12p35 deficiency alleviates kainic acid-induced hippocampal neurodegeneration in C57BL/6 mice.
The role of IL-12 in excitotoxic neurodegeneration of brain is largely unknown. To address this issue, we used the model of kainic acid (KA)-induced hippocampal injury in IL-12p35 knockout (KO) mice, a well-characterized model for human neurodegenerative diseases. After KA treatment, hippocampal neurodegeneration was significantly less severe in the IL-12p35 KO mice than in wild-type mice as demonstrated by reduced pathological changes and astrogliosis. One day after KA treatment, levels of F4/80 and CD86 expression on microglia were significantly lower in IL-12p35 KO mice than in wild-type mice analyzed by flow cytometry, indicating that IL-12p35 deficiency resulted in lower levels of microglial activation. Five days after KA treatment, CD86 expression on microglia of wild-type mice was still higher, whereas F4/80 expression in wild-type mice decreased and was similar to that in IL-12p35 KO mice. Because microglial activation is necessary for KA-induced neurodegeneration, the lower level of microglial activation in the absence of IL-12p35 may alleviate hippocampal injury in KO mice. In summary, this study indicates that IL-12 may play a critical role in excitotoxin-induced brain injury.
Chen
Zhiguo
Z
Division of Experimental Geriatrics, Department of Neurotec, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Duan
Rui-Sheng
RS
Concha
Q Hernan
QH
Wu
Qinyang
Q
Mix
Eilhard
E
Winblad
Bengt
B
Ljunggren
Hans-Gustaf
HG
Zhu
Jie
J
D000818:Animals; D001921:Brain / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018664:Interleukin-12 / Q000172:deficiency / Q000378:metabolism*; D053765:Interleukin-12 Subunit p35; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D021122:Protein Subunits / Q000172:deficiency / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; C508858:IL12A protein, human; D053765:Interleukin-12 Subunit p35; D021122:Protein Subunits; D019014:fas Receptor; D018664:Interleukin-12; D007608:Kainic Acid