Study of uranium transfer across the blood-brain barrier

Lemercier, V.; Millot, Xavier; Ansoborlo, É.; Ménétrier, Florence; Flüry-Hérard, A.; Rousselle, Ch.; Scherrmann, Jean‐Michel

doi:10.1093/oxfordjournals.rpd.a006232

Cited by 57 publications

(23 citation statements)

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“…Peak uranium concentrations occurred less than 8 h after injection in most brain regions, demonstrating that uranium enters the brain rapidly. This is consistent with a recent publication that reported 1000-fold increases in extravascular brain uranium following exposure to 5 tIM uranium for 2 min by in situ perfusion (Lemercier et al, 2003). The mechanism by which uranium enters the CNS is unknown, but is likely similar to that for divalent metals since most plasma uranium is present as the divalent uranyl ion ([UO 2 ] 2 +) (Cooper et al, 1982).…”

supporting

confidence: 91%

Multifactorial Assessment of Depleted Uranium Neurotoxicity

Jortner¹

2004

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Public reporting burden for this collection of Information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of Information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and Tables Abstracts Manuscripts Introduction This is a four-year study on the neurotoxic potential of depleted uranium (DU) in laboratory rats. Previous studies with Gulf War veterans and experimental animals exposed to embedded DU suggest that neurotoxicity may result from DU exposure (McDiarmid eta!. 2000; Pellmar eta/., 1999). The current investigation is designed to assess the neurotoxic potential of acute and chronic exposure to DU and the contribution of stress to expression of DU neurotoxicity and kinetics. All studies are being performed with adult male Sprague-Dawley rats. As noted in the Table below, the components of this project are as follows: 1-Dose-finding and preliminary toxicokinetic studies of DU. These were conducted in the Year 1 of the project 2-Pilot stress study-To obtain an optimal model of experimental stress for use in the acute and chronic DU exposure studies. This was done in Year 2 and Year 3. 3-Acute neurotoxicity of soluble DU (uranyl acetate)-To determine nervous system kinetics and toxicity of DU. This was a major focus in Year 3. The in-life portion was done, and the neurobehavioral and most of the neurochemical data were obtained and analyzed. Neuropathological studies of the brain were also performed in this year. Tissue uranium assays were done in part. 4-Long-term toxicity study-This will assess chronic exposures from implanted solid DU particles, a model of some Gulf War casualties. This study began in Year 3, and is in progress. STRESS THAT RESULTED IN MARKED, TRANSIENT ELEVATION OF PLASMA CORTICOSTERONE. CLINICAL, NEUROCHEMICAL AND PATHOLOGICAL STUDIES WERE UNDERTAKEN. MAJOR FINDINGS WERE TRANSIENT DECREASE IN DOPAMINE IN THE CAUDATE-PUTAMEN ON POST-DOSING DAY 3 IN THE HIGH DOSE, UNSTRESSED ANIMALS. THERE WERE DU-RELATED DECREASES IN MOTOR ACTIVITY, BODY WEIGHT GAIN AND FORELIMB GRIP STRENGTH. DU DOSE-RELATED RENAL TUBULAR NECROSIS WAS ALSO SEEN, AND MAY HAVE CONTRIBUTED TO THESE CLINICAL FINDINGS. STRESS HAD NO EFFECT ON THE RENAL DISEASE OR THE CLINICAL CHANGES, EXCEPT FOR A PROTECTIVE EFFECT IN THE GRIP STRENGTH. TASK 4, A LONG-TERM DU-IMPLANTATION/STRESS STUDY, WASMethods for both the acute and chronic (3, 4 -above) studies employed the following procedures. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis to assess the kinetics of uranium in the cerebral cortex, hippocampus, striatum, and cerebellum at selected periods after DU administration. Neurotoxicity is as...

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confidence: 91%

Multifactorial Assessment of Depleted Uranium Neurotoxicity

Jortner¹

2004

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“…In animals, it was demonstrated that U reached the CNS by blood circulation and microcirculation (Gilman et al 1998;Lemercier et al 2003). U levels increased significantly in the brains of rats implanted with depleted U pellets 1 month previously.…”

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confidence: 99%

Effect of U and ¹³⁷Cs chronic contamination on dopamine and serotonin metabolism in the central nervous system of the rat

Houpert

Lestaevel²,

Amourette³

et al. 2004

Can. J. Physiol. Pharmacol.

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Following the Chernobyl accident, the most significant problem for the population of the former Soviet Union for the next 50-70 years will be chronic internal contamination by radionuclides. One of the few experiments carried out in this field reported that neurotransmitter metabolism in the central nervous system of the rat was disturbed after feeding with oats contaminated by 137Cs for 1 month. The present study assessed the effect of chronic contamination by depleted U or 137Cs on the metabolism of two neurotransmitters in cerebral areas of rats. Dopamine and serotonin were chosen because their metabolism has been shown to be disturbed after external irradiation, even at moderate doses. Dopamine, serotonin, and some of their catabolites were measured by high-pressure liquid chromatography coupled with an electrochemical detector in five cerebral structures of rats contaminated over a 1-month period by drinking water (40 mg U.L -1 or 6500 Bq 137Cs.L -1). In the striatum, hippocampus, cerebral cortex, thalamus, and cerebellum, the dopamine, serotonin, and catabolite levels were not significantly different between the control rats and rats contaminated by U or 137Cs. These results are not in accordance with those previously described.

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“…For example, it has been shown that U is a developmental toxicant with dose-related fetal toxicity (Arfsten et al, 2001). U crosses the blood-brain barrier (Lemercier et al, 2003) and accumulates in the rat brain after chronic exposure (Pellmar et al, 1999a;Paquet et al, 2006), and several experimental studies have found that it has a toxic effect on the behavior of adult rats (Briner and Murray, 2005;Bellès et al, 2005;Houpert et al, 2005;Lestaevel et al, 2005). This behavioral toxicity is expressed by increased locomotor activity (Briner and Muray, 2005;Bellès et al, 2005), significantly decreased spatial working memory capacities , increased anxiety , and shorter paradoxical sleep .…”

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confidence: 99%

Uranium modifies or not behavior and antioxidant status in the hippocampus of rats exposed since birth

et al. 2015

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-In view of the known sensitivity of the developing central nervous system to pollutants, we sought to assess the effects of exposure to uranium (U) -a heavy metal naturally present in the environment -on the behavior of young rats and the impact of oxidative stress on their hippocampus. Pups drank U (in the form of uranyl nitrate) at doses of 10 or 40 mg.L -1 for 10 weeks from birth. Control rats drank mineral water. Locomotor activity in an open field and practice effects on a rotarod device decreased in rats exposed to 10 mg.L -1 (respectively, -19.4% and -51.4%) or 40 mg.L -1 (respectively, -19.3% and -55.9%) in compared with control rats. Anxiety (+37%) and depressive-like behavior (-50.8%) were altered by U exposure only at 40 mg.L -1 . Lipid peroxidation (+35%) and protein carbonyl concentration (+137%) increased significantly after exposure to U at 40 mg.L -1 . A significant increase in superoxide dismutase (SOD, +122.5%) and glutathione peroxidase (GPx, +13.6%) activities was also observed in the hippocampus of rats exposed to 40 mg.L -1 . These results demonstrate that exposure to U since birth alters some behaviors and modifies antioxidant status.

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Study of uranium transfer across the blood-brain barrier

Cited by 57 publications

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Multifactorial Assessment of Depleted Uranium Neurotoxicity

Multifactorial Assessment of Depleted Uranium Neurotoxicity

Effect of U and ¹³⁷Cs chronic contamination on dopamine and serotonin metabolism in the central nervous system of the rat

Uranium modifies or not behavior and antioxidant status in the hippocampus of rats exposed since birth

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Study of uranium transfer across the blood-brain barrier

Cited by 57 publications

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Multifactorial Assessment of Depleted Uranium Neurotoxicity

Multifactorial Assessment of Depleted Uranium Neurotoxicity

Effect of U and 137Cs chronic contamination on dopamine and serotonin metabolism in the central nervous system of the rat

Uranium modifies or not behavior and antioxidant status in the hippocampus of rats exposed since birth

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Effect of U and ¹³⁷Cs chronic contamination on dopamine and serotonin metabolism in the central nervous system of the rat