Participação das vias de sinalização da WNT na reconsolidação da memória de medo condicionado ao contexto e na consolidação da memória de reconhecimento social

Abstract

Aging is a process that causes physiological, psychological, and social changes, including a decline in organic and cognitive functions such as memory. Fear memories are essential for survival; however, when expressed out of context, they lead to different disorders, such as anxiety, phobias, and post-traumatic stress disorder. Yet, the social recognition memory is also important, as it refers to the ability to identify and recognize individuals of the same species, crucial for maintaining social bonds and survival. It is known that Wnt signaling pathways can modulate the physiology and functions of the hippocampus, prefrontal cortex and basolateral amygdala, and also directly alter the mechanisms involved in learning and memory. Furthermore, Wnt signaling interacts with NMDA receptors, facilitating the induction of long-term potentiation, a cellular model of learning and memory. Therefore, this study aims to investigate, in different brain structures, the participation of the Wnt/β-catenin and Wnt/Ca2+ pathway on the reconsolidation of fear memory in contextual fear conditioning (CFC) and the consolidation of social recognition memory (SRM). To evaluate the participation of Wnt in the reconsolidation of fear memory, adult male Wistar rats had cannulae implanted through stereotaxic surgery in the CA1 region of the dorsal hippocampus and were submitted to the CFC task. Thus, we found that inhibition of the canonical Wnt/β-catenin pathway with DKK1 in the CA1 region impaired CFC reconsolidation memory when administered immediately and 2 hours after the reactivation session. The same was not observed when administered 6 hours later; whereas inhibition of the non-canonical Wnt/Ca2+ signaling pathway, with SFRP1 immediately after the reactivation session had no effect. Furthermore, the impairment induced by the administration of DKK1 was blocked by the administration of the NMDA receptor agonist, D-Serine, immediately and 2h after the reactivation session. Therefore, we verified that the Wnt/β-catenin signaling pathway in the hippocampus is necessary to the reconsolidation memory of CFC at least two hours after reactivation, while the non-canonical Wnt/Ca2+ signaling pathway is not involved in this process, and that there is a relationship between the Wnt/β-catenin signaling pathway and NMDA receptors. To evaluate the participation of the Wnt/β-catenin and Wnt/Ca2+ signaling pathways on the consolidation of SRM, adult male rats, with guide cannulae implanted in the CA1 regions of the hippocampus, basolateral amygdala, and medial prefrontal cortex, were exposed to a juvenile (21 days) in the social discrimination task, and, 24 hours later, they underwent a test session in the presence of the previously presented juvenile and a new juvenile. It was observed that the administration of DKK1, immediately after the sample phase in the three regions studied, did not affect the consolidation of SRM. On the other hand, the administration of SFRP1, immediately after the sample phase, in the CA1 region of the hippocampus, blocked the consolidation of SRM; the same was not observed in the other two regions studied. Thus, these results demonstrate that the Wnt/β-catenin signaling pathway seems not to be involved in SRM consolidation, while the hippocampal Wnt/Ca2+ signaling pathway is necessary for SRM consolidation. Considering that it is extremely important to elucidate the mechanisms involved in the process of consolidation and reconsolidation of memories, the results obtained in this study allow to expand the understanding of the molecular processes involved in memories processing and in the development of drugs that aim to treat disorders involving fear and social recognition memories.