Date Published: June 1, 2018
Publisher: JKL International LLC
Author(s): Yali Chen, Mengmei Yin, Xuejin Cao, Gang Hu, Ming Xiao.
Both hypercholesterolemia and aging are related to cognitive decline or Alzheimer’s disease. However, their interactive influence on the neurodegenerative progress remains unclear. To address this issue, 6-month-old and 16-month-old female mice were fed a 3% cholesterol diet for 8 weeks, followed by hippocampus-related functional, pathological, biochemical and molecular analyses. The high cholesterol diet did not exacerbate age-dependent cognitive decline and hippocampal neuronal death, and even greatly mitigated decreases of synaptophysin and growth associated protein 43 expression in the hippocampus of aged mice. Compared with young controls, aged mice fed normal diet showed mild activation of hippocampal microglia with increased expression of CD68, a marker of the microglial M1 phenotype, and decreased expression of CD206, a marker of the microglial M2 phenotype. More interestingly, the high cholesterol diet not only improved NLRP3 inflammasome activation and IL-1β expression, but also increased levels of anti-inflammatory cytokines IL-4 and IL-6 in the hippocampus of old mice, suggesting playing pro- and anti-neuroinflammatory effects. In addition, the cholesterol rich diet resulted in a defect of the blood-brain barrier of aged hippocampus, as revealed by increased brain albumin content. These results have revealed both harmful and protective effects of high cholesterol diet on aged brain, which helps us to understand that hypercholesterolemia in the aged population is not associated with dementia and cognitive impairment.
The effect of cholesterol diet on neurodegeneration is controversial. A number of epidemiological studies have shown that hypercholesterolemia in midlife is related to an increased risk of developing AD or mild cognitive impairment in later life [8, 38]. However, other studies have suggested that high serum cholesterol levels are not associated with dementia and cognitive impairment in the elderly , and even decrease the risk of AD [39, 40]. But the underlying mechanisms for this discrepancy remain unclear. In order to clarify whether brain pathological changes induced by high cholesterol diet are age-differential, we have fed 6-month-old and 16-month-old female mice with the diet containing 3% cholesterol for 8 weeks, and examined corresponding changes in cognitive behavior, pathology and biochemistry.