Abstract: A significant body of evidence supports the multifactorial etiology of neurodevelopmental disorders (NDDs) affecting children. The present review focuses on early exposure to environmental chemicals as a risk factor for neurodevelopment, and presents the major lines of evidence derived from epidemiological studies, underlying key uncertainties and research needs in this field. We introduce the exposome concept that, encompassing the totality of human environmental exposures to multiple risk factors, aims at explaining individual vulnerability and resilience to early chemical exposure. In this framework, we synthetically review the role of variable gene backgrounds, the involvement of epigenetic mechanisms as well as the function played by potential effect modifiers such as socioeconomic status. We describe laboratory rodent studies where the neurodevelopmental effects of environmental chemicals are assessed in the presence of either a “vulnerable” gene background or adverse pregnancy conditions (i.e., maternal stress). Finally, we discuss the need for more descriptive and “lifelike” experimental models of NDDs, to identify candidate biomarkers and pinpoint susceptible groups or life stages to be translated to large prospective studies within the exposome framework.
Abstract: L-dopa is used to treat the motor symptoms associated with Parkinson’s disease, a neurodegenerative movement disorder characterized by a loss of dopamine neurons. L-dopa is the precursor to dopamine and crosses the blood-brain barrier to increase dopamine neurotransmission. This review will focus on the findings that dopamine produced from L-dopa is mediated in part by serotonin neurons. Direct evidence will be provided that increases in dopamine cause oxidative stress and damage serotonin neurons. Similarly, chronic L-dopa produces deficits in serotonin neurotransmission, including decreases in both serotonin cell bodies within the dorsal raphe and serotonin neurotransmitter concentrations in several forebrain regions. Since serotonin is involved in many important physiological processes including mood and cognition, L-dopa induced serotonin deficits may play a role in the side-effect symptoms observed in Parkinson’s disease patients treated with L-dopa.
Abstract: Understanding temporal changes in contaminant levels in coastal environments requires comparing levels of contaminants from the same species from different time periods, particularly if species are declining. Several species of shorebirds migrating through Delaware Bay have declined from the 1980s to the present. To evaluate some contaminants as cause for the declines, we examine levels of mercury, lead, cadmium, arsenic, chromium and selenium in feathers of red knot (Calidris canutus, N = 46individuals), semipalmated sandpiper (Calidris pusilla, N = 70) and sanderling (Calidris alba, N = 32) migrating through Delaware Bay, New Jersey, USA, from 1991 to 1992 (N = 40), 1995 (N = 28), and 2011–2012 (N = 80) to determine if levels have changed. We found: (1) arsenic, chromium, and lead increased in red knot and decreased in semipalmated sandpiper; (2) cadmium decreased in semipalmated sandpipers; (3) mercury decreased in red knot and sanderlings; (4) selenium decreased in red knot and increased in semipalmated sandpipers. In 2011/2012 there were significant interspecific differences for arsenic, mercury and selenium. Except for selenium, the element levels were well below levels reported for feathers of other species. The levels in feathers in red knots, sanderling, and semipalmated sandpipers from Delaware Bay in 2011/2012 were well below levels in feathers that are associated with effect levels, except for selenium. Selenium levels ranged from 3.0 µg·g−1 dry weight to 5.8 µg·g−1 (semipalmated sandpiper), within the range known to cause adverse effects, suggesting the need for further examination of selenium levels in birds. The levels of all elements were well below those reported for other marine species, except for selenium, which was near levels suggesting possible toxic effects.
Abstract: Mercury, cadmium, arsenic and lead are among priority metals for toxicological studies due to the frequent human exposure and to the significant burden of disease following acute and chronic intoxication. Among their common characteristics is chemical affinity to proteins and non-protein thiols and their ability to generate cellular oxidative stress by the best-known Fenton mechanism. Their health effects are however diverse: kidney and liver damage, cancer at specific sites, irreversible neurological damages with metal-specific features. Mechanisms for the induction of oxidative stress by interaction with the cell thiolome will be presented, based on literature evidence and of experimental findings.
Abstract: The C57BL/6 (B6) mouse is the background strain most frequently used for genetically-modified mice. Previous studies have found significant behavioral and genetic differences between the B6J (The Jackson Laboratory) and B6N substrains (National Institutes of Health); however, most studies employed only male mice. We performed a comprehensive battery of motor function and learning and memory tests on male and female mice from both substrains. The B6N male mice had greater improvement in the rotarod test. In contrast, B6J female mice had longer latencies to falling from the rotarod. In the Morris water maze (MWM), B6J males had significantly shorter latencies to finding the hidden platform. However, B6N females had significantly shorter path lengths in the reversal and shifted-reduced phases. In open field locomotor activity, B6J males had higher activity levels, whereas B6N females took longer to habituate. In the fear conditioning test, B6N males had a significantly longer time freezing in the new context compared with B6J males, but no significant differences were found in contextual or cued tests. In summary, our findings demonstrate the importance of testing both males and females in neurobehavioral studies. Both factors (sex and substrain) must be taken into account when designing developmental neurotoxicology studies.