EXCITOTOXIC NEURODEGENERATION INDUCED BY INTRANASAL ADMINISTRATION OF KAINIC ACID IN C57BL/6 MICE
Zhiguo Chena, Hans-Gustaf Ljunggrenb, Nenad Bogdanovica, Inger Nennesmoc, Bengt Winblada, Jie Zhua
aNEUROTEC, Division of Experimental Geriatrics,
bCenter for Infectious Medicine, Department of Medicine,
cDivision of Pathology, Karolinska Institutet, Huddinge
University Hospital, Stockholm, Sweden
Glutamate excitotoxicity plays a key role in inducing neuronal cell
death in many neurological diseases, such as Alzheimer's disease. 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.
Key words:
kainic acid, excitotoxic, neurodegeneration, hippocampus, C57BL/6 strain.
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