Excitotoxic neurodegeneration induced by 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, administration of kainic acid, an analogue of the excitotoxin glutamate, results in hippocampal cell death and seizures. Kainic-acid-induced seizures in mice provide a well-characterized model for studies of human neurodegenerative diseases. However, C57BL/6 mice, which are often used for genetic analyses and transgenic and knockout studies, are resistant to excitotoxicity induced by subcutaneous administration of kainic acid. In the present study, kainic acid administered by the intranasal route was shown to result in continuous tonic-clonic seizures in C57BL/6 mice. These seizures continued for 1-5 h and successfully induced selective lesions in area CA3 of the hippocampus. The survival rate was high even after mice experienced severe seizures. The hippocampal lesions were associated with a high level of cyclooxygenase-2 production as well as astrogliosis. Administration of kainic acid also altered behavioral responses, with mice showing a significant increase in locomotion and rearing activity as indicated by an open-field test. This animal model could provide a valuable tool for exploring the role of excitotoxicity in neuropathological conditions and should be further evaluated in gene-targeting studies of neurodegenerative diseases.
Chen
Zhiguo
Z
NEUROTEC, Division of Experimental Geriatrics, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Ljunggren
Hans-Gustaf
HG
Bogdanovic
Nenad
N
Nennesmo
Inger
I
Winblad
Bengt
B
Zhu
Jie
J
D000281:Administration, Intranasal; D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight; D051546:Cyclooxygenase 2; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000633:toxicity*; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D012640:Seizures / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D015996:Survival Rate
D018690:Excitatory Amino Acid Agonists; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D007608:Kainic Acid