Rieger Débora K, Costa Ana Paula, Budni Josiane, Moretti Morgana, Barbosa Sabrina Giovana Rocha, Nascimento Kyria S, Teixeira Edson H, Cavada Benildo S, Rodrigues Ana Lúcia S, Leal Rodrigo B
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
BioMolLab, Universidade Federal do Ceará, Fortaleza, CE 60455-970, Brazil.
Pharmacol Biochem Behav. 2014 Jul;122:53-60. doi: 10.1016/j.pbb.2014.03.008. Epub 2014 Mar 18.
Lectins recognize and reversibly bind to carbohydrates attached to proteins and lipids modulating a variety of signaling pathways. We previously showed that ConBr, a lectin from Canavalia brasiliensis seeds, produced an antidepressant-like effect in mice by modulating the monoaminergic neurotransmitter systems. Moreover, ConBr blocked hippocampal neurotoxicity induced by quinolinic acid in vivo and by glutamate in vitro, suggesting a neuroprotective activity of ConBr via glutamatergic system modulation. Therefore, the present study was undertaken to investigate the involvement of the N-methyl-D-aspartate (NMDA) receptor and the L-arginine-nitric oxide (NO) pathway in the antidepressant-like action displayed by ConBr in the forced swimming test (FST). With the aim of verifying the involvement of NMDA receptors in the antidepressant-like effect of ConBr (10 μg/site, i.c.v.), an intracerebroventricular (i.c.v.) pretreatment with either NMDA (0.1 pmol/site) or D-serine (30 μg/site) was carried out. The results show that both treatments blocked the effect of ConBr. Furthermore, the coadministration of subeffective doses of the NMDA receptor antagonist MK-801 (0.001 mg/kg, i.p.) or ketamine (0.1 mg/kg, i.p.; NMDA receptor antagonist) and ConBr (0.1 μg/site, i.c.v.) caused a synergistic reduction in immobility time. In order to verify the dependence of the L-arginine-NO-cGMP pathway, on the effect of ConBr in the FST, a pretreatment with the NO precursor, L-arginine (750 mg/kg, i.p.), or the PDE5 inhibitor, sildenafil (5 mg/kg, i.p.), was performed. Both drugs abolished the antidepressant-like action of ConBr. Finally, the administration of subeffective doses of the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 30 pmol/site, i.c.v.) and ConBr (0.1 μg/site, i.c.v.) produced a synergistic antidepressant-like effect in the FST. Taken together, the results suggest that the antidepressant-like effect of ConBr in the FST involves NMDA receptor inhibition and reduction in NO and cGMP synthesis.
凝集素能够识别并可逆地结合附着于蛋白质和脂质上的碳水化合物，从而调节多种信号通路。我们之前的研究表明，来自巴西刀豆种子的凝集素ConBr通过调节单胺能神经递质系统，在小鼠体内产生了类似抗抑郁的效果。此外，ConBr在体内可阻断喹啉酸诱导的海马神经毒性，在体外可阻断谷氨酸诱导的海马神经毒性，这表明ConBr通过调节谷氨酸能系统具有神经保护活性。因此，本研究旨在探讨N-甲基-D-天冬氨酸（NMDA）受体和L-精氨酸-一氧化氮（NO）途径在ConBr在强迫游泳试验（FST）中表现出的类似抗抑郁作用中的参与情况。为了验证NMDA受体在ConBr（10 μg/位点，脑室内注射）的类似抗抑郁作用中的参与情况，分别用NMDA（0.1 pmol/位点）或D-丝氨酸（30 μg/位点）进行了脑室内（i.c.v.）预处理。结果表明，这两种处理均阻断了ConBr的作用。此外，联合给予亚有效剂量的NMDA受体拮抗剂MK-801（0.001 mg/kg，腹腔注射）或氯胺酮（0.1 mg/kg，腹腔注射；NMDA受体拮抗剂）与ConBr（0.1 μg/位点，脑室内注射）可协同减少不动时间。为了验证L-精氨酸-NO-cGMP途径对ConBr在FST中作用的依赖性，分别用NO前体L-精氨酸（750 mg/kg，腹腔注射）或磷酸二酯酶5抑制剂西地那非（5 mg/kg，腹腔注射）进行了预处理。两种药物均消除了ConBr的类似抗抑郁作用。最后，联合给予亚有效剂量的可溶性鸟苷酸环化酶抑制剂1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ；30 pmol/位点，脑室内注射）与ConBr（0.1 μg/位点，脑室内注射）在FST中产生了协同的类似抗抑郁作用。综上所述，结果表明ConBr在FST中的类似抗抑郁作用涉及NMDA受体抑制以及NO和cGMP合成的减少。
