Increased microglial activation and astrogliosis after intranasal administration of kainic acid in C57BL/6 mice.
Glutamate excitotoxicity plays a key role in inducing neuronal cell death in many neurological diseases. In mice, intranasal administration of kainic acid (KA), an analogue of the excitotoxin glutamate, results in hippocampal cell death and provides a well-characterized model for studies of human neurodegenerative diseases. In this study, we describe neurodegeneration and gliosis following intranasal administration of KA in C57BL/6 mice. By using Nissl's staining, neurodegeneration was found in area CA3 of hippocampus, and neuronal apoptosis was demonstrated by enhanced FAS(CD95/APO-1) expression detected by immunohistochemistry and Western blotting. Astrogliosis was exhibited by increased glial fibrillary acidic protein (GFAP) expression in the hippocampus and cortex. We also studied the profile of molecular expression on microglia in C57BL/6 mice. One and 3 days after KA administration, CD45, F4/80, CD86, MHCII, iNOS but not CD40 expression was enhanced or induced on microglia. In summary, KA administration results in an early microglial activation and a prolonged astrogliosis in C57BL/6 mice.
Division of Experimental Geriatrics, Department of Neurotec, Karolinska Institute, Karolinska University Hospital, Stockholm 14186, Sweden. zhiguo.chen@neurotec.ki.se
Zhiguo
Z
Chen
Rui-Sheng
RS
Duan
Hernan Concha
HC
Quezada
Eilhard
E
Mix
Inger
I
Nennesmo
Abdu
A
Adem
Bengt
B
Winblad
Jie
J
Zhu
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002452:Cell Count / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D005434:Flow Cytometry / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced*; D007150:Immunohistochemistry / Q000379:methods; D007608:Kainic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D019014:fas Receptor / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D019014:fas Receptor; C036763:monocyte-macrophage differentiation antigen; D007608:Kainic Acid