Effects of differential contextual conditions or beta amyloid peptides infusion in the spatial memory and immediate early genes expression in hippocampus of rats exposed to Barnes maze
beta amyloid peptides; spatial memory; strategy; immediate early genes; c-Fos; Zif-268; hippocampus; Barnes maze.
The cause of Alzheimer’s disease (AD) remains uncertain, but the accumulation of amyloid peptides (A) is the main pathophysiological hallmark of the condition. Spatial deficit is considered an important initial sign of AD, as opposed to other types of memory impairment that arise in later stages. In our experiments, we evaluated the effects of brain infusion of A peptides on spatial and non-spatial strategies and immediate early genes hippocampal expression of rats tested in the Barnes maze. A peptides (0.5L/site/day; 30pmoL solution of A1-40:A1-42 10:1) or saline were bilaterally infused into CA1 (on the first treatment day) and intraventricularly (on the following 15 days) in six-month-old Wistar male rats. A infusion induced a deficit in the performance (increased latency and distance traveled to reach the target compared to saline group). In addition, a significant association between treatment and strategy used in retrieval was found: A group preferred the non-spatial strategy, while saline group presented preference for spatial strategy. Immunohistochemical c-Fos labeling performed after behavioral testing revealed decreased CA1 cell count in the A group, indicating reduction in neuronal activation of this region after spatial retrieval. However, A group also showed increased number of labeled cells in DG, suggesting the occurrence of compensatory mechanisms due to A treatment effect. There were no alterations in Zif-268 expression. In conclusion, the protocol of A infusion used here induced a subtle cognitive deficit that was specific to spatial aspects, compatible with prodromic characteristics of AD. Further, animals under A treatment presented some extent of retrieval, but using non-spatial strategies. Finally, an opposed pattern of effects of the treatment was observed in cell activation in different hippocampal subregions. Taken together, the results show subtle spatial memory alterations accompanied by modifications in hippocampal IEGs expression that are potentially relevant to future therapeutic approaches in the early stages of the disease.