Resumo

Lectins are carbohydrate-binding proteins that may recognize glycoconjugates on cell surface regulating a diversity of cell functions. Ionotropic glutamate receptors are glycosylated and may interact with endogenous lectins expressed in the brain. Nevertheless, the regulation of glutamatergic transmission by lectins is not well studied. We demonstrated previously that ConBr, a plant lectin isolated from Canavalia braziliensis seeds, displayed an antidepressant-like effect in vivo, in the forced swimming test in mice, by a mechanism that might involve NMDA receptor inhibition. In the present work it was investigated the possible in vitro neuroprotecting effect of ConBr against excitotoxic concentration of glutamate. Hippocampal slices were isolated from adult male mice and incubated for 4h in Krebs saline/DMEM buffer in the presence of glutamate (1 mM) or glutamate (1mM) plus ConBr (1, 10 or 100 μg/ml). Control slices were incubated only with the buffer or buffer plus lectin. The cell viability was measured by MTT. The results showed that glutamate caused a 30% (±2.2) decrease on hippocampal cell viability compared to control slices. ConBr, in a concentration-dependent manner, reversed the glutamate neurotoxicity. The maximum neuroprotective effect by ConBr was observed at 10μg/ml and the IC50 was 7.2μM. Moreover, it was evaluated the dependence of ConBr carbohydrate binding site for the neuroprotective action of this lectin. The results showed that preincubation with α-D-methyl-mannoside blocked the neuroprotective effect of ConBr against glutamate. In conclusion our findings indicate that ConBr, a glucose/mannose lectin, may inhibit glutamate neurotransmission, especially via NMDA receptors, by a mechanism dependent of carbohydrate binding. Therefore, it is possible to speculate that endogenous brain lectins with ConBr-like properties might modulate NMDA receptors and signaling pathways involved in events of neuroplasticity and neurotoxicity. Supported by CNPq, CAPES, FAPESC and FINEP