Prenatal exposure to methylmercury alters locomotor activity of male but not female rats

Abstract

In the present study the neurotoxic effects of a low dosage (0.5 mg/kg per day) of methylmercury (MeHg) on the developing nervous system were investigated. Pregnant rats were treated with MeHg from day 7 of pregnancy to day 7 of lactation. Locomotor activity (locomotion, rearing, and motility) and spatial learning ability were tested in the offspring at 6 months of age. The expression of tyrosine hydroxylase (TH) was examined by immunohistochemistry and in situ hybridization. A significant decrease in spontaneous motility and rearing was observed only in the MeHg-treated male rats. After administration of a low dose of d-amphetamine (0.5 mg/kg) no differences could be observed between control and MeHg-treated male rats, suggesting that changes in dopaminergic transmission were involved. However, no change in TH messenger RNA expression was observed. No changes in spatial learning acquisition or memory were shown in MeHg-treated rats. Taken together, these findings show that during development a very low dosage of MeHg exerts neurotoxic effects detectable in adulthood, and that susceptibility is gender-dependent.

Neurobehavioural functions in adult progeny of rat mothers exposed to methylmercury or 2,2', 4,4', 5,5'-hexachlorobiphenyl (PCB 153) alone or their combination during gestation and lactation

“…In mice, however, females are the affected gender [23]. In all the remaining tests of Experiment I, effects were found in males only, which is consistent with observations of other authors suggesting a higher vulnerability of male fetuses to the MeHg toxic action [24]. From the review paper by Castoldi et al [22], as well from the recent report by Ferraro et al [25] it appears that passive avoidance is the test situation in which the deficits produced by perinatal/prenatal MeHg exposure are commonly reported.…”

Methylmercury elicits rapid inhibition of cell proliferation in the developing brain and decreases cell cycle regulator, cyclin E

“…Our observations of cell cycle effects of MeHg in vivo occur at Hg levels (probablỹ 200-300ng/g, given use of 3mg/kg MeHg for proliferation studies and a measured level of 700-900ng/g after 10mg/kg) achieved with chronic dosing and also associated with long-term behavioral effects (Rossi et al, 1997;Newland and Reile, 1999;Sakamoto et al, 2002). Whether MeHg is delivered as a single injection (our study) or a chronic low dose oral exposure, similar mercury levels are associated with altered cell production and future behavioral effects (Rossi et al, 1997;Newland and Reile, 1999;Castoldi et al, 2001;Goulet et al, 2003).…”

“…Whether MeHg is delivered as a single injection (our study) or a chronic low dose oral exposure, similar mercury levels are associated with altered cell production and future behavioral effects (Rossi et al, 1997;Newland and Reile, 1999;Castoldi et al, 2001;Goulet et al, 2003). Significantly, Hg levels in human infants from fish-eating populations also range from 50-250ng/g (Lapham et al, 1995), suggesting that our injection model better approximates environmental exposures than the consequences of overt metal toxicity.…”

“…MeHg effects at earlier phases of the cell cycle have been identified but are less welldefined (Roy et al, 1991;Faustman et al, 2002). In addition, many MeHg studies on cellular toxicity (Castoldi et al, 2001), neurogenesis , and long-term effects (Goulet et al, 2003;Rossi et al, 1997;Sakamoto et al, 2002) have used chronic dosing or timepoints ≥ 24h. Few studies have investigated early, single-dose effects on neurogenesis.…”

Early developmental effects of separate or combined perinatal exposure to methylmercury (MeHg) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) in the rat

“…in the high dose group. The level of the low dose was based on data showing that at this exposure level, the mercury concentration in newborn rats was comparable to that found in human infants from populations with high dietary fish consumption [41,42].…”