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Enhancing Nuclear Safety


Research

The effects on health of chronic contamination with a low dose of radionuclides

(juillet 2011)

RESEARCH allowing the evaluation of radionuclide-related risks and their impact on health

The ENVIRHOM-Santé experimental research programme or Understanding the effects on health of chronic contamination with a low dose of radionuclides

The brain: A new target organ to uranium

Is the xenobiotic detoxification system affected by chronic exposure to uranium ?

Chronic ingestion of caesium 137 in a post-accident situation

Chronic exposure to caesium 137: Experimental and epidemiological studies

Metabolomics: Application in radiotoxicology

The perspectives of the ENVIRHOM-Santé programme

The brain: A new target organ to uranium


Philippe LESTAEVEL

Researcher at the Experimental radiotoxicology laboratory (LRTOX)

Transfer of uranium into the brain and its radiotoxicological consequences


The central nervous system (CNS) is the order system which controls all of the major physiological functions. Dysfunction of the latter can therefore impact upon the whole body. The CNS is also a major target in terms of toxic effects for some heavy metals such as mercury, manganese and lead. However, few studies have been conducted on the neurotoxicity of uranium, another heavy metal.

Transfer of uranium into the brain

In the case of acute or chronic exposure, it has been clearly shown that uranium crosses the blood-brain barrier (BBB) and passes into the brain depending on the dose received, the pathway of contamination and the duration of exposure to uranium (Fitsanakis et al., 2006). However, this blood brain transfer is still unknown. One study carried out by Lemercier et al, shows that uranium does not alter the BBB, which suggests a possible vascular transfer (Lermercier et al., 2003). The hypothesis that transporters could be involved via circulating proteins such as transferrin, apolipoprotein or albumin has not been validated.

figure 1

figure 1

The effects of 1.5 months’ exposure to depleted uranium (DU) or enriched uranium (EU) (2 mg/kg/day) on the central nervous system: Anxiety, paradoxal sleep, spatial memory, lipid peroxidation in the entorhinal cortex (marker of oxidative stress) and acetylcholinesterase activity in the hippocampus. Interactions between the various effects observed are highlighted with a red arrow; the data are expressed in averages ± SEM (standard error of the mean)*: p<0.05; ** :p<0.01.


Enriched uranium affects cognitive behaviour and the sleep cycle to a greater extent than depleted uranium sources

Uranium has numerous effects at cognitive level. Our experimental studies in the rat have shown a reduction of 10 to 20% in short-term memory following chronic contamination with 4% enriched uranium (EU) for 1.5 and 9 months (2 mg/kg/day via drinking water) (Houpert et al., 2005; Houpert et al., 2007) as shown in Figure 1. Conversely, the same contamination protocol carried out with depleted uranium (DU) was devoid of significant effect (Houpert et al., 2005). Other studies have shown that the learning processes of the location of an immersed platform (Morris water test) seem reduced following chronic ingestion of DU but at concentrations higher than those used in our experiments (10, 20 or 40 mg/kg/day, 3 months and 80 mg/kg, 4 weeks) (Albina et al., 2005).

We have also shown a disorder in the wake-sleep cycle following the ingestion of EU (2 mg/kg/day via drinking water). However, this was not observed with DU. In fact, an increase in the quantity of paradoxal sleep following sub-chronic contamination of 1 and 2 months’ duration were observed (+47% and +66%, respectively). This increase disappeared when contamination was extended to 3 months (Lestaevel et al., 2005). This result suggests an adaptive response. Moreover, the anxiety of rats is increased after 1.5 months’ contamination with EU whereas contamination with DU has no effect (Houpert et al., 2005). Together, these results highlight the importance of the radiological toxicity of uranium.

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