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Glucocorticoid receptors (GRs) exert actions on the hippocampus that are important for memory formation. There are correlations between vascular dysfunctions and GR-related gene expression. Both vascular dysfunction and GR gene expression decline occur during the ageing process. Therefore, hypotensors, which have effects on improving vascular dysfunction, may be able to ameliorate GR gene expression decline in ageing mice and improve ageing-mediated memory deficits. In this study, we hypothesized that hypotensors could alleviate the decline of GR gene expression and ameliorate age-induced learning and memory deficits in a d-gal-induced ageing mice model. In line with our hypothesis, we found that chronic d-gal treatment decreased GR and DCX expression in the hippocampus, leading to learning and memory deficits. Amlodipine (AM) and puerarin (PU) treatment improved GR gene expression decline in the hippocampus and ameliorated the learning and memory deficits of d-gal-treated mice. These changes correlated with enhanced DCX expression and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Furthermore, PU treatment conveyed better effects than AM treatment, but combination therapy did not enhance the effects on improving GR expression. However, we did not find evidence of these changes in non- d-gal-treated mice that lacked GR gene expression decline. These results suggest that AM and PU could improve d-gal-induced behavioural deficits in correlation with GR gene expression. [ABSTRACT FROM AUTHOR]

Previous studies have shown that polyphenols might be potent neuroprotective agents in Drosophila melanogaster, a valid model for PD, acutely treated with oxidative stress-stimulants. This study report for the first time that polyphenols exposure prolong life span ( P < 0.05 by log-rang test) and restore locomotor activity (i.e., climbing capability, P < 0.05 by χ test) of Drosophila melanogaster chronically exposed to paraquat compared to flies treated with paraquat alone in 1% glucose. We found that (10%) glucose partially prolongs life span and climbing in Drosophila exposed to iron, PQ or in combination, suggesting that both stimuli enhance a movement disorder in a concentration-dependent and temporal-related fashion. Moreover, chronic exposure of (1 mM) PQ/(0.5 mM) iron synergistically affect both survival and locomotor function independently of the temporal order of the exposure to the toxicants, but the survival is modulated in a concentration and temporal fashion by glucose. This investigation is the first to report that Ddc- GAL4 transgenic flies chronically fed with polyphenols increase life span ( P < 0.05 by log-rang test) and enhance movement abilities ( P < 0.05 by χ test) compared to untreated Ddc- GAL4 or treated with paraquat in 1% glucose. Our present findings support the notion that Drosophila melanogaster might be a suitable model to study genetic, environmental and nutritional factors as causal and/or modulators in the development of PD. Most importantly, according to our model, we have demonstrated for the first time chronic polyphenols exposure as potential therapeutic compounds in the treatment of PD. These findings altogether open new avenues for the screening, testing and development of novel antioxidant drugs against oxidative stress stimuli. [ABSTRACT FROM AUTHOR]