Abstract
The cause of Alzheimer’s disease (AD) remains uncertain. The accumulation of amyloid peptides (Aβ) is the main pathophysiological hallmark of the disease. Spatial deficit is an important initial sign of AD, while other types of memory impairments that appear in later stages. The Barnes maze allows the detection of subtle alterations in spatial search by the analysis of use of different strategies. Previous findings showed a general performance deficit in this task following long-term (35 days) infusion of Aβ, which corresponds to the moderate or severe impairments of the disease. In the present study, we evaluated the effects of a low-dose 15-day long treatment with Aβ peptides on spatial and non-spatial strategies of rats tested in the Barnes maze. Aβ peptides (0.5 μL/site/day; 30 pmoL solution of Aβ1–40:Aβ1–42 10:1) or saline were bilaterally infused into the CA1 (on the first treatment day) and intraventricularly (on the following 15 days) in 6-month-old Wistar male rats. Aβ 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 search strategy in the retrieval trial was found: Aβ group preferred the non-spatial search strategy, while saline group preferred the spatial search. In conclusion, the protocol of Aβ infusion used here induced a subtle cognitive deficit that was specific to spatial aspects. Indeed, animals under Aβ treatment still showed retrieval, but using non-spatial strategies. We suggest that this approach is potentially useful to the study of the initial memory deficits in early AD.
Highlights
Alzheimer disease (AD) is a neurodegenerative disorder characterized by atypical neural activity, dysfunction and loss of synapses and neurons, accompanied by progressive cognitive decline (Braak et al, 1992; West et al, 1994; Eustache et al, 2004; Sadek et al, 2004)
Spatial deficits detected in navigation tasks have been proposed as an important initial sign of AD, and this feature distinguishes this condition from other types of age-related cognitive impairments (Lithfous et al, 2013)
The comparison of means of percentage of strategies in the groups in the whole probe session showed that saline group used possible search strategies (spatial, t(4) = −0.636, p = 0.559; non-spatial, t(4) = 0.685, p = 0.531), while the Aβ group preferred non-spatial search strategies (spatial, t(8) = −3.020, p = 0.017; non-spatial, t(8) = 3.121, p = 0.014; Figure 5D). We observed that both groups showed reduced distance and latency to reach target and number of errors, and increased percent time in the target quadrant across the trainings, indicating that all the animals learned the task (Barnes, 1979; Pompl et al, 1999)
Summary
Alzheimer disease (AD) is a neurodegenerative disorder characterized by atypical neural activity, dysfunction and loss of synapses and neurons, accompanied by progressive cognitive decline (Braak et al, 1992; West et al, 1994; Eustache et al, 2004; Sadek et al, 2004). Barnes Maze and Amyloid Peptide peptides has been suggested as the cause of cytotoxicity This accumulation is the basis of the amyloid cascade hypothesis for AD and precedes the first manifestations of cognitive decline (Braak and Braak, 1991; Hardy and Selkoe, 2002; Desikan et al, 2013; Sperling et al, 2011, 2014). Recent studies have investigated human spatial learning and memory in virtual reality environments (Iaria et al, 2009; Head and Isom, 2010; Plancher et al, 2010) This approach has been useful to show age-related cognitive hippocampal dysfunctions, to studies in rodent models (McNaughton et al, 1989; Poucet et al, 1991; McDonald and White, 1993; Pouzet et al, 2002). Deficits in other types of memory usually arise in later stages of the disease progression (Sá et al, 2012; Tarawneh and Holtzman, 2012)
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