Role of Nitric Oxide in Domoic Acid Induced Hippocampal Degeneration
Journal Title: Journal of Neurological Sciences-Turkish - Year 2007, Vol 24, Issue 1
Abstract
We used a mouse model of domoic acid (DA)-induced temporal lobe epilepsy to determine if nitric oxide (NO) has anticonvulsant properties. The protective effects of NO were assessed using acute and chronic doses of DA (ip) in the presence and absence of NO synthase (NOS) inhibitors. The Institute of Cancer Research mice treated with different doses of DA (1-6mg/kg body weight) showed dose dependent stereotypic neurological signs, which were enhanced by pretreatment with NOS inhibitors. Further, mice sacrificed after 30 and 60 days of DA treatment showed reactive glial cells with large cell bodies and long processes in CA1 and CA2 regions of the hippocampus. These changes were more pronounced in groups treated with neuronal NOS inhibitor especially in 60 days treatment group. In addition, immunohistochemistry and Western blot analysis demonstrated loss of calcium binding protein calbindin D28k immunoreactivity in the hippocampal regions of animals treated with DA plus NOS inhibitors reflecting damage to calbindin rich neurons in the hippocampus. Our findings suggest that a single sub-acute dose of DA can cause progressive damage to the hippocampus, which is markedly influenced by NOS inhibitors. Further, this study establishes that NO agonists may have a therapeutic value in treating patients with temporal lobe epilepsy.
Authors and Affiliations
Manju PANDE, Avery HARPS, Mecheri SUNDARAM, Parminder VIG
Keywords
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