Summary
The kynurenine pathway intermediate 3-hydroxyanthranilic acid (3-HANA) is converted by 3-HANA 3,4-dioxygenase (3-HAO) to the putative neuropathogen quinolinic acid (QUIN). In the present study, the neuroprotective effects of the 3-HANA analogue and 3-HAO inhibitor NCR-631 was investigated using organotypic cultures of rat hippocampus. An anoxic lesion was induced by exposing the cultures to 100% N2 for 150 min, resulting in a pronounced loss of pyramidal neurons, as identified using NMDA-R1 receptor subunit immunohistochemistry. NCR-631 provided a concentration-dependent protective effect against the anoxia. NCR-631 was also found to counteract the loss of pyramidal neurons in two models of neuroinflammatory-related damage; incubation with either LPS (10 ng/ml) or IL-1β (10 IU/ml). The findings suggest that NCR-631 has neuroprotective properties and that it may be a useful tool to study the role of kynurenines in neurodegeneration.
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Abbreviations
- EAA:
-
excitatory amino acid
- 3-HANA:
-
3-hydroxyanthranilic acid
- 3-HAO:
-
3-hydroxyanthranilic acid 3,4-dioxygenase
- IL-1β :
-
interleukin-1β
- KYNA:
-
kynurenic acid
- LPS:
-
lipopolysaccaride
- NCR-631:
-
4,6-dibromo-3hydroxyanthranilic acid
- NMDA:
-
N-methyl-d-aspartate
- QUIN:
-
quinolinic acid
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Luthman, J., Radesäter, A.C. & Öberg, C. Effects of the 3-hydroxyanthranilic acid analogue NCR-631 on anoxia-, IL-1β- and LPS-induced hippocampal pyramidal cell lossin vitro . Amino Acids 14, 263–269 (1998). https://doi.org/10.1007/BF01345273
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DOI: https://doi.org/10.1007/BF01345273