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Effects of COX inhibitors on neurodegeneration and survival in mice exposed to the marine neurotoxin domoic acid.
- Source :
-
Neuroscience letters [Neurosci Lett] 2011 Jan 03; Vol. 487 (1), pp. 83-7. Date of Electronic Publication: 2010 Oct 08. - Publication Year :
- 2011
-
Abstract
- The marine neurotoxin domoic acid (DA) is a rigid analogue of the neurotransmitter glutamate and a potent agonist of kainate subtype glutamate receptors. Persistent activation of these receptor subtypes results in rapid excitotoxicity, calcium-dependent cell death, and neuronal degeneration in regions of the brain where glutamatergic pathways are concentrated. Previous work has shown that DA promotes the expression of inflammatory genes in the brain, such as cyclooxygenase 2 (COX2). To investigate the impact of inflammation on the development of neurodegeneration, and ultimately survival following DA administration, we used selective (L745337, Merck) and non-selective (acetylsalicylic acid (ASA)) COX inhibitors in DA exposed mice. Adult male ICR mice were given a regime of either ASA or L23547 both before and after a single LD50 dose of DA. Mice were observed immediately after toxin introduction and then sacrificed at 2 days post exposure. Our lower dose of L23547 increased survival and was most effective at decreasing neuronal degeneration in the CA1 and CA3 regions of the hippocampus, areas especially sensitive to DA excitotoxicity. This study shows that COX2 plays a role in DA induced neurodegeneration and death, and that inhibitors may be of value for treatment in human and wildlife DA exposure.<br /> (Published by Elsevier Ireland Ltd.)
- Subjects :
- Animals
Cell Survival drug effects
Disease Models, Animal
Drug Administration Schedule
Hippocampus pathology
Kainic Acid analogs & derivatives
Kainic Acid toxicity
Lethal Dose 50
Male
Mice
Mice, Inbred ICR
Neurodegenerative Diseases chemically induced
Neurodegenerative Diseases mortality
Neurodegenerative Diseases pathology
Neurotoxins toxicity
Aspirin therapeutic use
Cyclooxygenase Inhibitors therapeutic use
Indans therapeutic use
Neurodegenerative Diseases drug therapy
Neurons drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7972
- Volume :
- 487
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neuroscience letters
- Publication Type :
- Academic Journal
- Accession number :
- 20934488
- Full Text :
- https://doi.org/10.1016/j.neulet.2010.10.001