Reduction of Amyloid Angiopathy and Aβ Plaque Burden after Enriched Housing in TgCRND8 Mice

Abstract

Alzheimer's disease (AD) is the most prevalent form of senile dementia worldwide. It is characterized by two major histological hallmarks: senile plaques, ie, extracellular deposits mainly consisting of ␤-amyloid (A␤), and neurofibrillary tangles, ie, intracellular accumulations of hyperphosphorylated tau protein.1 AD patients show progressing cognitive decline as well as noncognitive behavioral symptoms such as wandering, sleep disturbance, and physical aggression.2 There are various risk factors for AD including age, family history, or apolipoprotein E 4 genotype.3 Epidemiological studies additionally suggest that the amount of time spent on intellectual and physical activities negatively correlates with the extent of cognitive decline and even risk of developing AD. 4,5 Although it cannot be excluded that lower activity levels are early subclinical symptoms, one should consider them also as a risk factor. In line with this assumption is the use of cognitive training as a rehabilitative measure resulting in deceleration of dementia progress. However, the underlying molecular pathways are essentially unknown.In laboratory rodents cognitive, physical, and social stimulation can be regulated by altering housing conditions. It is well established that living in an enriched environment provided by additional structural or social stimuli may increase locomotor and exploratory activity, improve learning and memory performance, increase dendritic sprouting and synapse formation in the neocortex and hippocampus as well as neurogenesis in the dentate gyrus, 6 and affects behavioral, endocrinological, and immunological parameters.7 Environmental enrichment also facilitates recovery from acute brain lesions,

Amyloid-β Oligomers Induce Differential Gene Expression in Adult Human Brain Slices

“…3), has also been described as part of AD pathogenesis (22,68). One of the genes grouped in this pathway is cullin 3, which encodes an essential component of the ubiquitin E3 ligase complex.…”

Nurturing brain plasticity: impact of environmental enrichment

“…189 A reduction in brain b-amyloid deposition after EE exposure has also been shown in APP, TgCRND8 and AD11 transgenic mice. 186,187,190,191 Some studies have also investigated the effects of EE on neurogenesis in AD mouse models. Although conditional PS1 knockout mice and mice overexpressing either wild-type human PS1 or the mutant form P117L show a deficiency in EE-induced neurogenesis, [192][193][194] it has been recently reported that EE promotes hippocampal neurogenesis in APP and TgCRND8 mice.…”

Effects of voluntary exercise on structure and function of cortical microvasculature

“…Regular aerobic exercise has been shown to enhance performance on cognitive tasks in aged humans [1][2][3][4][5][6] and in learning and memory tests in animals. [7][8][9][10][11][12][13] In addition, physical exercise may be protective against Alzheimer's disease 8,9,[14][15][16][17][18][19][20] and may enhance recovery from both stroke [21][22][23][24][25] and traumatic brain injury. 11 However, the changes in brain morphology and function underlying these effects remain incompletely understood.…”