Feeding mice with diets containing mercury-contaminated fish flesh from French Guiana: a model for the mercurial intoxication of the Wayana Amerindians.

BACKGROUND: In 2005, 84% of Wayana Amerindians living in the upper marshes of the Maroni River in French Guiana presented a hair mercury concentration exceeding the limit set up by the World Health Organization (10 microg/g). To determine whether this mercurial contamination was harmful, mice have been fed diets prepared by incorporation of mercury-polluted fish from French Guiana. METHODS: Four diets containing 0, 0.1, 1, and 7.5% fish flesh, representing 0, 5, 62, and 520 ng methylmercury per g, respectively, were given to four groups of mice for a month. The lowest fish regimen led to a mercurial contamination pressure of 1 ng mercury per day per g of body weight, which is precisely that affecting the Wayana Amerindians. RESULTS: The expression of several genes was modified with mercury intoxication in liver, kidneys, and hippocampus, even at the lowest tested fish regimen. A net genetic response could be observed for mercury concentrations accumulated within tissues as weak as 0.15 ppm in the liver, 1.4 ppm in the kidneys, and 0.4 ppm in the hippocampus. This last value is in the range of the mercury concentrations found in the brains of chronically exposed patients in the Minamata region or in brains from heavy fish consumers. Mitochondrial respiratory rates showed a 35-40% decrease in respiration for the three contaminated mice groups. In the muscles of mice fed the lightest fish-containing diet, cytochrome c oxidase activity was decreased to 45% of that of the control muscles. When mice behavior was assessed in a cross maze, those fed the lowest and mid-level fish-containing diets developed higher anxiety state behaviors compared to mice fed with control diet. CONCLUSION: We conclude that a vegetarian diet containing as little as 0.1% of mercury-contaminated fish is able to trigger in mice, after only one month of exposure, disorders presenting all the hallmarks of mercurial contamination.

Long-term consequences of soman poisoning in mice: part 2. Emotional behavior.

The organophosphorus compound soman produces long-lasting epileptic seizure activity which is associated to brain damage, more particularly in the hippocampus and the amygdala. The companion paper (see part 1 in the same journal issue) describes the neuropathology in the amygdala of soman-poisoned mice. The present paper examines the long-term effects of soman poisoning on emotional reactivity in mice, 30 or 90 days after intoxication using behavioral tasks involving amygdala function. The emotional behavior was estimated in animal tests of unconditioned fear (light/dark boxes, elevated plus-maze) and conditioned fear (auditory and contextual response). In the light/dark boxes and elevated plus-maze, mice intoxicated with soman (110 microg/kg, 1.2 LD(50)) showed an anxiety-like behavior profile at post-poisoning days 30 and 90. In conditioned fear, results showed that both auditory and contextual conditioned responses are increased on post-soman day 30 but no longer on post-soman day 90, evidencing behavioral recovery overtime. This latter behavioral result is in accordance with the delayed neuronal regeneration patterns described in the companion paper (part 1).

Modafinil restores memory performance and neural activity impaired by sleep deprivation in mice.

The original aims of our study have been to investigate in sleep-deprived mice, the effects of modafinil administration on spatial working memory, in parallel with the evaluation of neural activity level, as compared to non-sleep-deprived animals. For this purpose, an original sleep deprivation apparatus was developed and validated with continuous electroencephalography recording. Memory performance was evaluated using spontaneous alternation in a T-maze, whereas the neural activity level was estimated by the quantification of the c-Fos protein in various cerebral zones. This study allowed altogether: First, to evidence that a diurnal 10-h sleep deprivation period induced an impairment of spatial working memory. Second, to observe a decrease in c-Fos expression after sleep deprivation followed by a behavioural test, as compared to non-sleep-deprived mice. This impairment in neural activity was evidenced in areas involved in wake-sleep cycle regulation (anterior hypothalamus and supraoptic nucleus), but also in memory (frontal cortex and hippocampus) and emotions (amygdala). Finally, to demonstrate that modafinil 64 mg/kg is able to restore on the one hand memory performance after a 10-h sleep deprivation period, and on the other hand, the neural activity level in the very same brain areas where it was previously impaired by sleep deprivation and cognitive task.