Lectins are
proteins capable of reversible binding to
carbohydrates or
glycoconjugates. In the central nervous system of mammals,
lectins with affinity for
mannose/
glucose or
galactose can modulate cellular communication.
ConBr, a
lectin isolated from the seeds of Canavalia brasiliensis, previously showed
antidepressant effect in the forced swimming test in mice, with involvement of the monoaminergic system. In this study, we investigated the
neuroprotective effects of
ConBr against
quinolinic acid (QA), a well-known
NMDA agonist that produces severe neurotoxicity when administered in vivo.
ConBr (10 μg/site) administered via intracerebroventricular (i.c.v.) showed a neuroprotective activity against
seizures induced by QA (36.8 nmol/site; i.c.v.) when administered 15 min prior to QA, with a percentage of protection around 50%.
ConBr was also able to significantly decrease the severity of the
seizures but without changes in the latency of the first convulsion or the duration of the
seizures. This effect was dependent on the structural integrity of the
ConBr protein and its binding capacity to
oligosaccharides residues. ConA, a
lectin with high similarity to
ConBr, did not reverse the QA-induced
seizures. Moreover,
ConBr was able to protect against hippocampal cell death caused by QA, which was measured by
propidium iodide incorporation. QA caused activation of JNK2 and improved the phosphorylation of Ser831 and 845 on the
AMPA receptor GluR1 subunit, and both of these effects were counteracted by
ConBr. Our data suggest that the
lectin ConBr may exert a modulatory action on
NMDA receptors, which inhibits its activity in response to QA.