Bilberry anthocyanins improve neuroinflammation and cognitive dysfunction in APP/PSEN1 mice via the CD33/TREM2/TYROBP signaling pathway in microglia.

Alzheimer's disease, characterized by neuroinflammation and beta-amyloid protein plaques, is a memory-threatening neurodegenerative disease with no effective treatment. Here, the effect of bilberry anthocyanins (BA) on cognitive functions was evaluated using APP/PSEN1 transgenic Alzheimer's disease model mice and their WT littermates. Our results revealed that BA appreciably improves learning and memory abilities and reverses defects to cognitive functions in APP/PSEN1 mice. Furthermore, BA reverses brain, liver and kidney damage caused by Alzheimer's disease, with no significant changes in oxidative stress and lipid metabolism-related indicators. In addition, BA decreases serum and brain lipopolysaccharide (LPS) levels and increases fecal short-chain fatty acid content. Immunofluorescence and RT-PCR analysis results showed that BA fully activates the microglia and astrocytes, downregulates the expression of inflammatory factors (TNF-α, NF-Kß, IL-1ß, IL-6, COX-2, iNOS and CD33) and chemokine receptor CX3CR1, and upregulates the expression of microglia homeostatic factors (TREM2 and TYROBP) and Toll-like receptors (TLR2 and TLR4). Moreover, western blot analysis revealed that BA significantly upregulates the expression of synaptic and phagocytotic function-related proteins (CD68, synaptophysin and IRF7) in APP/PSEN1 mice. Altogether, we show for the first time that BA consumption reverses Alzheimer's disease-induced cognitive disfunction, decreases hippocampal neuroinflammatory responses, and induces phagocytosis of microglia to beta-amyloid protein plaques by regulating the CD33/TREM2/TYROBP signaling pathway in microglia.

Reduction of Aging-Induced Oxidative Stress and Activation of Autophagy by Bilberry Anthocyanin Supplementation via the AMPK-mTOR Signaling Pathway in Aged Female Rats.

Oxidative-stress-induced senescence constitutes a great risk factor for chronic diseases. Therefore, ameliorating oxidative-stress-induced senescence is expected to prevent chronic diseases. The beneficial effects of bilberry anthocyanin (BA) on healthy aging were evaluated using 12 month old, aging female SD rats in this study. The experimental results suggested that consumption of a middle-dose of BA (MBA) appreciably increased the relative liver mass by 7.34% when compared with that of the AC group. Furthermore, BA significantly increased the total antioxidant capacity, total superoxide dismutase activity, and catalase activities; decreased malondialdehyde, serum low-density lipoprotein cholesterol (LDL-C), serum total cholesterol (TC), serum triglyceride (TG), and glycated serum protein (GSP) levels; and reduced TC/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios. In addition, MBA decreased the activity of fecal bacterial enzymes and increased the content of fecal short-chain fatty acids. The Western blot results showed that MBA significantly upregulated the expression of OCLN, ZO-1, and autophagy-related proteins (ATP6 V0C, ATG4D, and CTSB) in aging rats. Moreover, it also showed that MBA induced the phosphorylation of AMPK and FOXO3a and inhibited the phosphorylation of mTOR, which indicated that bilberry anthocyanin induced autophagy via the AMPK-mTOR signaling pathways. This induction of autophagy further promoted oxidative stress resistance effects and intestinal epithelial barrier function of bilberry anthocyanin in aging female rats.

Bilberry anthocyanin extract promotes intestinal barrier function and inhibits digestive enzyme activity by regulating the gut microbiota in aging rats.

This study was aimed at understanding potential mechanisms regarding bilberry anthocyanin extract consumption and healthy aging and the effects on intestinal barrier function and digestive enzyme activity, through regulating the gut microbiota in aging rats. Medium-dose bilberry anthocyanin extract consumption (20 mg per kg bw per day) was the optimum amount to regulate the intestinal function of aging rats. After consumption, bacteria beneficial to the intestine (Aspergillus oryzae, Lactobacillus, Bacteroides, Clostridiaceae-1, the Bacteroidales-S24-7-group and the Lachnospiraceae_NK4A136_group) were induced to grow, and harmful bacteria (Verrucomicrobia and Euryarchaeota) were inhibited. However, high-dose bilberry anthocyanin extract consumption altered some intestinally beneficial bacteria in an adverse way. There was a correlation between changes in bacterial composition and changes in short-chain fatty acids and the intestinal mucosal barrier. Bilberry anthocyanin extract consumption also decreased the activity of digestive enzymes. Our results suggest that bilberry anthocyanin extract consumption is a potential approach for assisting healthy aging.

[Depressive symptoms and related factors among primary and middle school students in Changfeng county of Anhui province:a two-year longitudinal study].

OBJECTIVE: To assess the prevalence of depressive symptoms, trends on its longitudinal development and related influencing factors among primary and middle school students in Changfeng county of Anhui province. METHODS: Through cluster sampling methods, all students from 3 to 9 grades in 5 primary schools and 3 middle schools in Changfeng county of Anhui province were investigated through questionnaire as subjects of baseline survey in December 2009. Subjects of this longitudinal study were students in grades 3, 4 and 7 at the time of the baseline survey and were contacted once a year for two years. At last, a total of 816 students participated in all the three surveys. A structured questionnaire including Children's Depression Inventory, socio-demographic characteristics and some potential influential factors was employed for this study. A Generalized Estimating Equation (GEE) was used to evaluate the related influencing factors of children's depressive symptoms in the longitudinal study. RESULTS: Prevalence rates of depressive symptoms were 11.3% , 10.4% and 8.5% , respectively, at the baseline, 1-year and 2-year follow-up studies, among primary and middle school students. Scores on depressive symptoms of total subjects and children who had always been left at home in the follow-up process showed significant differences at the three surveys (F = 13.423, P < 0.001; F = 5.761, P = 0.003). 25 percent of the 92 students who showed depressive symptoms at the baseline survey remained those depressive symptoms at the 1-year follow-up study and 87 percent of the 23 students who had depressive symptoms at the baseline and 1-year follow-up surveys still showing depressive symptoms at the 2-year follow-up study. Results from the GEE program indicated that grade 3 students, having syblings, family with dysfunction or at low level of self-esteem etc., were prone to development while sex and parents' educational level were not correlated with depressive symptoms. CONCLUSION: Prevalence of depressive symptoms among primary and middle school students in Changfeng county of Anhui province appeared a decreasing tendency during the follow-up process in our study. Through the longitudinal development, we noticed that the prevalence of depressive symptoms seemed to be related to the personal characteristics, education and family environment of the subjects under our study. Improving the level of family function as well as individual's self-esteem might positively contribute to mental health of those primary and middle school students.