Evidence that exposure to methyl mercury during gestation induces behavioral and neurochemical changes in offspring of rats

Cagiano, R.; Salvia, Maria Antonietta De; Renna, G.; Tortella, E.; Braghiroli, Daniela; Parenti, Carlo; Zanoli, Paola; Baraldi, Mario; Annau, Zoltan; Cuomo, V.

doi:10.1016/0892-0362(90)90108-o

Cited by 61 publications

(45 citation statements)

References 11 publications

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“…One of the most frequent findings related to prenatal MM exposure is represented by learning and memory deficit (2)(3)(4)(5), which was confirmed and expanded also by our groups (6,7). The learning and memory deficits were described as a consequence of a single prenatal exposure to the metal at different stages of gestation.…”

supporting

confidence: 56%

“…In this context, it is worth noting that children with evident neurological symptoms are born from asymptomatic mothers exposed to MM. Evidence have been provided by many researchers that a single prenatal administration of MM to rats during late gestation produces cognitive deficits, represented mainly by learning and memory disturbances (2,3,6,7,9). The cognitive deficits found in adult rats prenatally exposed to MMC are associated with changes in several neurotransmitter systems, comprising mainly the opiatergic and the glutamatergic systems, which seem to undergo long-lasting alterations.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous demonstrations that MMC exposure changes the characteristics of NMDA receptors (6) and increases the levels of quinolinic acid, an endogenous agonist of these receptors that potentially exerts neurotoxic effects, seem to implicate this excitatory neurotransmission system in the neurological brain dysfunction associated with MMC exposure. The altered level of NR-2B mRNA in the hippocampus may reflect a modification of the ontogenetic regulation of NMDA receptor type 2 subunit NR-2B.…”

Section: Discussionmentioning

confidence: 99%

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Cognitive deficits and changes in gene expression of NMDA receptors after prenatal methylmercury exposure.

Baraldi

Zanoli

Tascedda

et al. 2002

Environ Health Perspect

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Previous studies showed learning and memory deficit in adult rats that were prenatally exposed to methylmercury chloride (MMC) in an advanced stage of pregnancy (15 days). Under these conditions, the cognitive deficits found at 60 days of age paralleled particularly changes in the N-methyl-D-aspartate (NMDA) receptor characteristics. In the present study, we report the behavioral effects of a single oral dose of MMC (8 mg/kg) administered earlier at gestational day 8. The use of different learning and memory tests (passive avoidance, object recognition, water maze) showed a general cognitive impairment in the in utero-exposed rats tested at 60 days of age compared with matched controls. Considering the importance of the glutamatergic receptor system and its endogenous ligands in learning and memory process regulation, we surmised that MMC could affect the gene expression of NMDA receptor subtypes. The use of a sensitive RNase protection assay allowed the evaluation of gene expression of two families of NMDA receptors (NR-1 and NR-2 subtypes). The result obtained in 60-day-old rats prenatally exposed to MMC, showed increased mRNA levels of the NR-2B subunit in the hippocampus but not in the frontal cortex. The data suggest that the behavioral abnormalities of MMC-exposed rats might be ascribed to a neurotoxic effect of the metal that alters the gene expression of a specific NMDA receptor subunit in the hippocampus.

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supporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Cognitive deficits and changes in gene expression of NMDA receptors after prenatal methylmercury exposure.

Baraldi

Zanoli

Tascedda

et al. 2002

Environ Health Perspect

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“…In a series of studies by Annau, Cuomo, and co-workers (92)(93)(94), rats were given 5 to 8 mg/kg MM (po) on day 8 or 15 of pregnancy; open field activity at various postnatal ages was apparently not affected. The role of test factors, however, is suggested by the results of another study in the same series (95), which showed hyperactivity at 4 to 15 days with a different test using a closed activity cage.…”

Section: Methylmercury (Mm) As Early Asmentioning

confidence: 99%

Economical test methods for developmental neurobehavioral toxicity.

Bignami

1996

Environ Health Perspect

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“…In addition, developmental exposure to MeHg causes transient increases in receptor sensitivity (Cagiano et al, 1990), reduces monoamine oxidase (MAO) activity in the brainstem (Beyrouty et al, 2006) and increases dopamine (DA) neurotransmitter levels, DA uptake, and DA turnover (Bartolome et al, 1982;Bartolome, Whitmore, Seidler, & Slotkin, 1984). These studies suggest that disruption of DA neurotransmission is a consequence of developmental exposure to MeHg.…”

mentioning

confidence: 99%

Gestational methylmercury exposure selectively increases the sensitivity of operant behavior to cocaine.

Reed¹,

Newland²

2009

Behavioral Neuroscience

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Developmental methylmercury (MeHg) exposure alters dopamine neurotransmitter systems, but the selectivity of this and the effects of low, environmentally relevant MeHg exposure regimens are poorly understood. In previous reports, some including littermates of animals studied here, chronic, low-level exposures affected performance on reversal tasks and enhanced reinforcer efficacy. Using high-and low-rate operant behavior under a fixed interval (FI) schedule, sensitivity was examined to drugs that target noradrenergic and dopaminergic neurotransmitter systems. Female rats were exposed in utero to 0, 0.5, or 5 ppm of mercury, as MeHg, via maternal drinking water. Selenium (Se) is thought to attenuate MeHg's neurotoxicity, so animals consumed a diet containing 0.06 or 0.6 ppm of Se. At 11 months, they lever-pressed under a FI 120" schedule of sucrose reinforcement. Acute dose-effect curves were generated with cocaine, desipramine, SKF-38393, quinpirole, SCH-23390, and sulpiride. As compared with unexposed animals, those exposed to 5 ppm mercury, regardless of Se exposure, were 2 to 3 times more sensitive to the rate-reducing effects of high doses of cocaine and did not show increased responding earlier in the interval following moderate cocaine doses. Cocaine's effects in the 0.5 ppm Hg groups depended on dietary Se: low Se diet resulted in a rightward shift in the DEC compared to controls, whereas a high Se diet did not. No differential effects of MeHg were seen with the other drugs. Gestational MeHg exposure produces irreversible sensitivity to dopamine, but not norepinephrine, reuptake inhibitors and not to drugs that target D 1 or D 2 receptors.

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Evidence that exposure to methyl mercury during gestation induces behavioral and neurochemical changes in offspring of rats

Cited by 61 publications

References 11 publications

Cognitive deficits and changes in gene expression of NMDA receptors after prenatal methylmercury exposure.

Cognitive deficits and changes in gene expression of NMDA receptors after prenatal methylmercury exposure.

Economical test methods for developmental neurobehavioral toxicity.

Gestational methylmercury exposure selectively increases the sensitivity of operant behavior to cocaine.

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