Participação das vias de sinalização Wnt/Β-catenina e Wnt/Ca2+ do córtex pré-frontal medial na memória de medo condicionado ao contexto

Abstract

Aging is a process which incurs physiological, psychological and social changes, including vulnerability to neurodegenerative disorders and memory deficits. The Wnt signaling pathways are involved in memory formation in the hippocampus, albeit its role in other memory-related regions, such as the medial prefrontal cortex (mPFC) is still to be elucidated. In this paper, we investigate the involvement of Wnt’s signaling pathways in the medial prefrontal cortex, in the processes of acquisition, consolidation and retrieval, associated with fear memory. Towards that goal, male Wistar rats were subjected to a contextual fear conditioning protocol (CFC) and were injected with DKK1 and SFRP1, which are Wnt antagonists of the canonical Wnt/β-catenin and non-canonical Wnt/Ca2 pathways, respectively, in the prelimbic (PrL) subdivision of the mPFC, in different moments, and acquisition, consolidation and retrieval of short- and long-term memory were assessed. We observed that the blockade of the canonical Wnt/β-catenin, and non-canonical Wnt/Ca2, signaling pathways 15 minutes before, or immediately after, the CFC task training, did not affect short- (STM) and long-term memory (LTM); however, when the blockade occurred 15 minutes before the retention test, it impaired the retrieval of short and long-term, memory. These findings highlight the importance of the mPFC in the retrieval of fear memory, showing that both the canonical Wnt/β-catenin and the non-canonical Wnt/Ca2+ pathways are necessary for this process. The understanding of cerebral systems act on fear memories might provide a new target for the treatment of disorders related to fear memories, such as post-traumatic stress disorder and other anxiety disorders.