Kainic acid-induced excitotoxic hippocampal neurodegeneration in C57BL/6 mice: B cell and T cell subsets may contribute differently to the pathogenesis.
The roles of T cells and B cells in kainic acid (KA)-induced hippocampal lesions were studied in C57BL/6 mice lacking specific T cell populations (CD4, CD8, and CD4/CD8 cells) and B cells [Igh-6(-/-)]. At 48 mg/kg of KA administrated intranasally, KA-induced convulsions were seen in all groups. However, CD4/CD8(-/-) mice exhibited the mildest seizures; the responses of CD8(-/-), Igh-6(-/-) and wild-type mice were intermediate, whereas CD4(-/-) mice displayed much more severe clinical signs and 100% early mortality, indicating that a deficiency of CD4 T cells obviously increased susceptibility to KA-induced brain damage. Histopathological analysis of the mice that survived 7 days after KA administration revealed that CD4/CD8(-/-) mice had the fewest pathologic changes but Igh-6(-/-) mice showed more severe lesions in area CA3 of the hippocampus than CD8(-/-) and wild-type mice. Reactive astrogliosis were prominent in all KA-treated mice. Locomotor activity as assessed by open-field test increased after KA administration in Igh-6(-/-) and wild-type mice only. These results denote the influence of the adaptive immune response on KA-induced hippocampal neurodegeneration and suggest that B cell and T cell subsets may contribute differently to the pathogenesis.
Chen
Zhiguo
Z
Division of Experimental Geriatrics, Department of Neurotec, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Yu
Shuo
S
Concha
Hernan Q
HQ
Zhu
Yu
Y
Mix
Eilhard
E
Winblad
Bengt
B
Ljunggren
Hans-Gustaf
HG
Zhu
Jie
J
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D006624:Hippocampus / Q000276:immunology* / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D009498:Neurotoxins; D012640:Seizures / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D009498:Neurotoxins; D007608:Kainic Acid