Abstract
Alzheimer’s disease (AD) is associated with a progressive dementia, and there is good evidence that it is more pronounced in individuals that have fewer stimuli during their lives. Environmental stimulation promotes morphological and functional changes in the brain, leading to amplification of cognitive functions, and has been described in humans and animals. In this study, we evaluated the effects of enriched environment (EE) stimulation on spatial memory and senile plaque formation in transgenic mice PDGFB-APPSwInd (TG) that overexpress the human amyloid precursor protein, normally resulting in an increased density of senile plaques. We compared this group of EE stimulated transgenic mice (TG-EE) with an EE stimulated control group of age-matched C57Bl/6 wild type animals (WT-EE). Both groups were exposed to EE stimulation between the ages of 8 and 12 months. As controls of the experiment, there were a group of TG mice not exposed to EE (TG-Ctrl) and a group of WT mice not exposed to EE (WT-Ctrl). The TG-EE group presented improved spatial memory when compared to the TG-Ctrl animals. In addition, the TG-EE group showed a 69.2% reduction in the total density of senile plaques in the hippocampus when compared to the TG-Ctrl group. In this group, the concentration of senile plaques was greater in the dorsal part of the hippocampus, which is linked to spatial localization, and the reduction of this density after the submission to EE was as high as 85.1%. EE stimulation had no effect on the density of amyloid-β (Aβ) oligomers. However, amyloid scavenger receptor class B member 1 (SR-B1) density was significantly decreased in the TG-Ctrl mice, but not in the TG-EE mice, suggesting that cognitive stimulation had an effect on the formation of a cognitive reserve that could prevent the accumulation of senile plaques. It is suggested that the stimulation of old mice by EE for 4 months led to the formation of brain resilience that protected the brain from the deposition of senile plaques, one of the hallmarks of AD, leading to improvement in spatial memory.
Highlights
Alzheimer’s disease (AD) is a progressive and fatal neurodegenerative process and pharmacological therapy can only delay its progression or reduce some symptoms
On the probe day of the spatial memory evaluation, it was observed a significant increase in time to enter the escape box in the WT-EE (4.6 times, P < 0.01), transgenic mice PDGFB-APPSwInd (TG)-Ctrl (3.5 times, P < 0.05) and TG-EE (4.0 times, P < 0.01) groups, when compared to the WT-Ctrl animals (46.5 ± 15.8 s; Figure 1)
In order to verify if the greater time observed in the WT-EE, TG-Ctrl and TG-EE groups to enter the escape box on the probe day was related to an increase in motor activity, the animals were submitted to an activity cage immediately after the end of the Barnes maze observations
Summary
Alzheimer’s disease (AD) is a progressive and fatal neurodegenerative process and pharmacological therapy can only delay its progression or reduce some symptoms. The clearance of Aβ to reduce the amyloid load is one of the strategies that has been proposed to promote a better quality of life for AD patients (Wyss-Coray et al, 2001; Bates et al, 2009; Xin et al, 2018). It is believed that increases in this load precede the onset of the disease by approximately 20 years. There has been an increase in the number of studies related to strategies to reduce the disease progress and improve quality of life, mainly related to cognitive aspects (Duara et al, 2009; Ghezzi et al, 2013; Cummings et al, 2017)
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