Environmental enrichment ameliorated high-fat diet-induced Aβ deposition and memory deficit in APP transgenic mice

Abstract

The pathogenesis of Alzheimer's disease (AD) is tightly associated with metabolic dysfunctions. In particular, a potential link between type 2 diabetes (T2DM) and AD has been suggested epidemiologically, clinically, and experimentally, and some studies have suggested that exercise or dietary intervention reduces risk of cognitive decline. However, there is little solid molecular evidence for the effective intervention of metabolic dysfunctions for prevention of AD. In the present study, we established the AD model mice with diabetic conditions through high-fat diet (HFD) to examine the effect of environmental enrichment (EE) on HFD-induced AD pathophysiology. Here, we demonstrated that HFD markedly deteriorated memory impairment and increased β-amyloid (Aβ) oligomers as well as Aβ deposition in amyloid precursor protein (APP) transgenic mice, which was reversed by exposure to an enriched environment for 10 weeks, despite the continuation of HFD. These studies provide solid evidence that EE is a useful intervention to ameliorate behavioral changes and AD pathology in HFD-induced aggravation of AD symptoms in APP transgenic mice.

Exercise Is More Effective than Diet Control in Preventing High Fat Diet-induced β-Amyloid Deposition and Memory Deficit in Amyloid Precursor Protein Transgenic Mice

“…mice-In our recent study, voluntary exercise is shown to be a useful tool for preventing the progress of cognitive dysfunction and amyloid pathology in APP-HFD mice (7). Notably, voluntary exercise does not ameliorate HFD-induced hyperinsulinemia or hypercholesterolemia but improves glucose intolerance as well as cognitive impairment.…”

“…For example, a prospective study revealed that physical activity is protective against the development of cognitive impairment in AD and that the highest activity group showed a lowered incidence of AD (9). Recently, we also demonstrated that voluntary exercise ameliorates HFD-induced memory deficit and A␤ deposition in APP transgenic mice (7), indicating that interventions to reduce metabolic conditions can become the preventive method for AD. However, it still remains unknown what kind of intervention targeting metabolic conditions is more effective.…”

“…The filter trap assay was conducted as described previously (7,12). Briefly, the protein concentration of the cerebrum samples in Tris-buffered saline (TBS)-extracted fraction was measured, and an equal amount of protein was subjected to vacuum filtration through a 96-well dot blot apparatus (Bio-Rad Laboratories) containing 200-nm pore size nitrocellulose membrane.…”

“…Experimental studies also support this idea. For example, application of HFD for APP transgenic mice exacerbated pathological alterations in the brain and their memory deficits (6,7). In contrast, it is widely known that composite dietary patterns such as the Mediterranean diet, characterized by high intake of vegetables, unsaturated fatty acids, and wine, are related to lower risk for AD (8).…”

“…In the present study, we used the AD model mice with metabolic conditions through HFD (APP-HFD mice), which we had previously established (7). In addition to voluntary exercise, we preventively conducted diet control or the combination of diet control with exercise using APP-HFD mice followed by comparing the effect of these interventions on cognitive function and amyloid pathology.…”