Reduced susceptibility to kainic acid-induced excitoxicity in T-cell deficient CD4/CD8(-/-) and middle-aged C57BL/6 mice.
Kainic acid (KA)-induced hippocampal injury is a good model for studying human neurodegenerative diseases. To investigate the roles of immune cells and age related changes in neurodegeneration, we used this model to assess reactions in young and middle-aged wild-type and CD4/CD8(-/-) mice by intranasal administration of KA. We found that CD4/CD8-deficiency resulted in a significant reduction of the severity of clinical signs and pathological changes in KA-treated young, but not in KA-treated middle-aged mice. Middle-aged wild-type mice had a similar reaction to KA insult as young and middle-aged CD4/CD8(-/-) mice. CD4/CD8(-/-) mice exhibited decreased locomotor and rearing activities as they approached to middle-aged state, which was not seen in wild-type mice. In addition, CD4/CD8-deficiency and increased age prevented KA-induced increase of both locomotor and rearing activities. The results suggest that a decline of immunological function is associated with aging, and both of them may contribute to the relative resistance to KA-induced neurotoxicity.
Chen
Zhiguo
Z
Division of Experimental Geriatrics, Department of Neurotec, Huddinge University Hospital, Stockholm, Sweden.
Ljunggren
Hans-Gustaf
HG
Zhu
Shun-Wei
SW
Winblad
Bengt
B
Zhu
Jie
J
D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015704:CD4 Antigens / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D007608:Kainic Acid / Q000633:toxicity*; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D007608:Kainic Acid