A stereotaxic atlas of the rat brain

Lead has been recognized as a poison for millennia and has been the focus of public health regulation in much of the developed world for the better part of the past century. The nature of regulation has evolved in response to increasing information provided by vigorous scientific investigation of lead's effects. In recognition of the particular sensitivity of the developing brain to lead's pernicious effects, much of this legislation has been addressed to the prevention of childhood lead poisoning. The present review discusses the current state of knowledge concerning the effects of lead on the cognitive development of children. Addressed are the reasons for the child's exquisite sensitivity, the behavioural effects of lead, how these effects are best measured, and the long-term outlook for the poisoned child. Of particular importance are the accumulating data suggesting that there are toxicological effects with behavioural concomitants at exceedingly low levels of exposure. In addition, there is also evidence that certain genetic and environmental factors can increase the detrimental effects of lead on neural development, thereby rendering certain children more vulnerable to lead neurotoxicity. The public health implications of these findings are discussed.

Lead neurotoxicity in children: basic mechanisms and clinical correlates.

Mercury neurotoxicity: Mechanisms of blood-brain barrier transport

In vivo Body Composition Studies.

Despite several decades of research on the neurotoxicology of lead and its continued prominence as a major environmental and occupational health hazard, the mechanisms of its toxic action in the nervous system are still unknown. The differential effects of lead exposure in young children and adults, as well as inconsistencies between in vivo and in vitro studies, suggest that lead toxicity may have multiple mechanisms in the central nervous system (CNS). Two are: neurodevelopmental toxicity, possibly involving interference with cell adhesion molecules, resulting in miswiring of the CNS during early development and possibly permanent dysfunction; and neuropharmacological toxicity, which might involve interactions between lead and calcium and lead and zinc, resulting in interference with neurotransmission at the synapse. This may be reversible.

Mechanisms of lead neurotoxicity, or looking beyond the lamppost.

The effect of chronic low level lead exposure on blood-brain barrier function in the developing rat.

Methylmercuric chloride was given to rats in a neurotoxic dose regimen (six daily doses of 8 mg kg−1 p.o.). During the silent (asymptomatic) phase of intoxication, the rates of cerebral glucose influx and cerebral glucose phos-phorylation were measured simultaneously using 2-deoxy-glucose. Regional cerebral blood flow was also measured using iodoantipyrine. The unidirectional flux of glucose into brain was not affected by methylmercury, and differences in the rates of glucose phosphorylation from region to region remained coupled to the regional cerebral blood flow. However, the blood flow was reduced throughout the brain, an observation suggesting that the operational level of metabolically regulated blood flow had been reset. Thus, in spite of a generalised reduction in blood flow, there was no indication of impaired cerebral glucose supply or utilization during the silent phase of methylmercury intoxication.

Regional cerebral glucose metabolism and blood flow during the silent phase of methylmercury neurotoxicity in rats.

Abstract Objectives Dietary components high in fiber have been shown to uniquely influence the gut microbiome through growth of beneficial bacteria. To determine if fiber from a pulse source (pea fiber) improves microbiome profiles, we tested the hypothesis that a high-fiber (HiFi) diet will result in improvements in microbial composition and diversity compared to a low-fiber (LowFi) diet. Methods In a parallel arm, repeated-measures design, overweight or obese adult males and females with at least one characteristic of the metabolic syndrome, were randomly assigned to consume a standard diet consisting of 25g/d (HiFi) or 5g/d (LowFi) of added pea fiber for 4 weeks (HiFi: n = 5, mean ± SD, BMI 30.1 ± 2.4 kg/m2, 30.6 ± 9.9 y; LowFi: n = 5, BMI 28.6 ± 3.4 kg/m2, 32.2 ± 11.7 y). The intervention meals were matched for palatability, energy, and macronutrient composition. Fecal sampling was performed on days 0, 7, 14, 21, and 28 of the intervention for a total of 50 samples. Gut microbiome composition was assessed by 16S rRNA amplicon sequencing. Results Alpha diversity as assessed by the Shannon index remained unchanged in both the HiFi and LowFi groups after 4 weeks. Beta diversity analysis (by Principal Coordinates) demonstrated that there was a statistically significant difference in microbial composition between the HiFi and LowFi group (p = 0.0001, F = 4.04) but no significant effect of time (p = 1, F = 0.28). There were differences seen in the microbial taxa in both groups at day 0 in comparison to the days after. For example, members of the genus Blautia, and Subdoligranulum (belonging to the phylum Firmicutes, known producers of short chain fatty acids (SCFA)) were low at day 0 in the HiFi group but increased from day 7 through day 28. These genera were unchanged in the LowFi group. Conclusions These preliminary results provide evidence of differential effects of HiFi compared to LowFi diets on the gut microbiome, particularly an increase in SCFA producers with HiFi. Funding Sources University of Missouri and NIH-K01- NHLBI.

https://academic.oup.com/cdn/article-pdf/6/Supplement_1/996/44040781/nzac069.001.pdf

Brenda P. Eley

Papers

The effect of chronic low level lead exposure on blood-brain barrier function in the developing rat.

Regional cerebral glucose metabolism and blood flow during the silent phase of methylmercury neurotoxicity in rats.

Gut Microbiome Responses to a 4-Week High-Fiber Feeding: Preliminary Findings