Early-life Pb exposure as a potential risk factor for Alzheimer's disease: are there hazards for the Mexican population?

Alzheimer's disease (AD) is the main cause of dementia in elderly. Increasing life expectancy is behind the growing prevalence of AD worldwide with approximately 45 million cases currently documented and projection studies suggesting a triplication of this number by 2050. Mexico does not have an accurate AD registry, but 860,000 cases were reported in 2014 and the prediction reaches 3.5 million cases by 2050. Amyloid plaques and neurofibrillary tangles represent the main hallmarks of AD, being constituted of amyloid beta (Aß) peptide and phosphorylated tau, respectively. The risk factors for AD include genetic mutations, lifestyle and environmental pollution. Particularly, lead (Pb) has attracted attention due to its ability to target multiple pathways involved in the pathophysiology of AD. Although the epidemiological data are limiting, animal and in vitro studies show growing evidence of causal effects of Pb exposure on AD-linked features including Aß aggregation and tau phosphorylation. Interestingly, many Pb effects occur selectively following early-life exposure to the metal, suggesting an epigenetic mechanism. This hypothesis is supported by changes in DNA methylation and microRNA expression patterns inflicted by early-life Pb exposure. Pb pollution in Mexico represents a significant problem because past and current mining activities, historical use of Pb as fuel additive and culturally rooted use of Pb in glazed ceramics, contribute to high levels of Pb pollution in Mexico. In this review we will discuss potential risks of AD development in Mexican populations chronically exposed to Pb in their childhood.

Cadmium Stress Leads to Rapid Increase in RNA Oxidative Modifications in Soybean Seedlings.

Increase in the level of reactive oxygen species (ROS) is a common response to stress factors, including exposure to metals. ROS over-production is associated with oxidation of lipids, proteins, and nucleic acids. It is suggested that the products of oxidation are not solely the markers of oxidative stress but also signaling elements. For instance, it has been shown in animal models that mRNA oxidation is a selective process engaged in post-transcriptional regulation of genes expression and that it is associated with the development of symptoms of several neurodegenerative disorders. In the present study, we examined the impact of short-term cadmium (Cd) stress on the level of two RNA oxidation markers: 8-hydroxyguanosine (8-OHG) and apurinic/apyrimidinic sites (AP-sites, abasic sites). In the case of 8-OHG, a significant increase was observed after 3 h of exposure to moderate Cd concentration (10 mg/l). In turn, high level of AP-sites, accompanied by strong ROS accumulation and lipid peroxidation, was noted only after 24 h of treatment with higher Cd concentration (25 mg/l). This is the first report showing induction of RNA oxidations in plants response to stress factors. The possible signaling and gene regulatory role of oxidatively modified transcripts is discussed.