TNF-alpha receptor 1 deficiency enhances kainic acid-induced hippocampal injury in mice.
The exact role of TNF-alpha in excitotoxic neurodegeneration of the brain is unclear. To address this issue, the kainic acid (KA)-induced hippocampal injury model, a well-characterized model of human neurodegenerative diseases, was used in TNF-alpha receptor 1 (TNFR1)-knockout (TNFR1-/-) mice in the present study. After nasal application of a single dose of 40 mg of KA per kilogram body weight, TNFR1-/- mice showed significantly more severe seizures than the wild-type mice. In addition, obvious neurodegeneration, enhanced microglia activation, and astrogliosis in the hippocampus, as well as increased locomotor activity, were found in TNFR1-/- mice compared with the wild-type controls 8 days after KA delivery. Moreover, CC chemokine receptor 3 expression on activated microglia was increased 3 days after KA treatment in TNFR1-/- mice, as measured by flow cytometry. These data suggest that TNF-alpha may play a protective role through TNFR1 signaling.
Lu
Ming-Ou
MO
Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
Zhang
Xing-Mei
XM
Mix
Eilhard
E
Quezada
Hernan Concha
HC
Jin
Tao
T
Zhu
Jie
J
Adem
Abdu
A
D000818:Animals; D001522:Behavior, Animal; D001930:Brain Injuries / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D039481:CD11b Antigen / Q000378:metabolism; D016022:Case-Control Studies; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency*; D012640:Seizures / Q000139:chemically induced
D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D047888:Receptors, Tumor Necrosis Factor, Type I; D007608:Kainic Acid