Alterações no perfil de expressão de genes em células hipocampais de camundongos (Mus musculus) induzidas por lectinas de Canavalia brasiliensis (ConBr) e Vatairea macrocarpa (VML) sugerem diferentes efeitos sobre a neuroplasticidade

Abstract

The nervous system regulates every aspect of the human body functions, and its complexity seems to be unlimited. Billions of neurons, clustered by distinct functions, constantly assess our anatomic inner conditions and surroundings factors, as light, pressure, sound, equilibrium, visual images, compounds concentrations, pain, emotions, consciousness, etc. The acquirement of new memories induces precise alterations on the neuronal guidance sum and intensity. The brain region where the memory formation is most studied is the hippocampus. The gene expression is rigorously controlled by the central nervous system. This space-time control is not only an efficient mechanism to functional neuronal net, but also to adjust this system in response to the acquisition of new information. The synapses alterations are known as neuroplasticity, a wide term that includes variations in the neuronal circuit, i.e. creation, exclusion, weakening, strengthening, etc. Most of our current knowledge on

neuroplasticity and memory formation is from two antagonistic phenomenons, the long- term potentiation (LTP) and the long-term depression (LTD). The LTP is usually divided

in two temporal distinct phases, the early (E-LTP) and late LTP (L-LTP). The E-LTP depends on preexistent proteins and last only a few minutes. Conversely, the L-LTP persists for several hours or days, requiring gene transcription and protein synthesis. The expression of several known genes, as BDNF, c-fos, c-jun, Arc, SNAP25, etc., is associated to neuroplasticity. Lectins are non-immune proteins that recognize and bind to carbohydrate specific structural epitopes. The aims of the present study was to assess the effect of the lectins from Canavalia brasiliensis and Vatairea macrocarpa (Leguminosae) seeds on the expression of key genes in hippocampus cell metabolism, and to evaluate these lectins potential on the neuroplasticity and neuroprotection. For this, the time-dependent expression levels (1, 6, 12 and 12 h) of the following genes

were analyzed: BDNF (Total and three alternative transcripts), TrkB, Arc, SNAP25, c- fos, c-jun, EAAT1, EAAT2, Lgals1, Lgals3, NR1, NR2A, NR2B, BAD, BCL2, COX2 e

HO1. The obtained results demonstrate that the VML treatment, after 1 h induced the expression of the genes BDNF (exon 1), Arc, c-fos, Lgals1, Lgals3, NR2B, BAD, BCL2 and Cox-2. BAD and COX2 up-regulation suggest that the VML is probably involved in an inflammatory process modulation. Nonetheless, in a general context, this lectin down-regulated the expression of several important genes to neuronal functioning and neuroplasticity. On the other hand, the ConBr treatment, predominantly after 12 h,

induced an intense increase in the BDNF expression, as well as the transcripts from TrkB, SNAP25, c-fos, c-jun and other genes, suggesting an augmented neuronal activity and neuroplasticity induction. Moreover, ConBr up-regulated EAAT1 and EAAT2 expression, indicating that this lectin could exerts a role on glutamate homeostasis, preventing excitotoxicity. Besides, it is worth pointing out that ConBr did not induced BAD and COX2 genes expression. Considering the obtained results, it can be concluded that ConBr, but not VML, has a strong biotechnological potential to modulate neuroplasticity, to act in neuroprotection and to regulate neuronal activity.