Chronic effects of methylmercury on the cerebral function in rats

Shigematsu, Junya; Yasuda, Takaaki; Goto, Yoshinobu; Tanaka, Kaoru; Tobimatsu, Shozó

doi:10.1016/s0022-510x(00)00454-8

Cited by 8 publications

(7 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown mild functional abnormalities and normal morphological findings in the CNS of chronically MeHg-exposed rats that show f axonal degeneration in peripheral sensory nerves [46,47]. Skin biopsies enabled the evaluation of sensory nerve axon terminals in the present study.…”

Section: Discussionmentioning

confidence: 74%

“…Sensorimotor and related neurological deficits, including paralysis, hind-limb crossing, and unsteady gait, can be induced in adult rodents [11,41,46,47]. In animal models, as in humans, the effects show a latent period, and can be highly persistent after both high [41] and more moderate [11] exposure levels.…”

Section: Introductionmentioning

confidence: 99%

“…These clinical observations and animal studies suggest that peripheral nerves are especially vulnerable. Short term exposure to 5 mg/kg/day, of MeHg, s.c., for 25 days, produced no detectable histopathology in cerebellum or visual cortex, a reversible decrease of local cerebral glucose utilization, the sparing of motor fibers, but permanent axonal degeneration in myelinated sensory peripheral nerve fibers [46,47]. Motor nerves are not invulnerable, however, as muscle atrophy was observed in 21% of Minamata victims [53], with short-term, high dose exposure correlated with extensive motor fiber damage [49].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dietary selenium protects against selected signs of aging and methylmercury exposure

et al. 2010

View full text Add to dashboard Cite

Acute or short-term exposure to high doses of methylmercury (MeHg) causes a well-characterized syndrome that includes sensory and motor deficits. The environmental threat from MeHg, however, comes from chronic, low-level exposure, the consequences of which are poorly understood. Selenium (Se), an essential nutrient, both increases deposition of mercury (Hg) in neurons and mitigates some of MeHg's neurotoxicity in the short term, but it is unclear whether this deposition produces longterm adverse consequences. To investigate these issues, adult Long Evans rats were fed a diet containing 0.06 or 0.6 ppm of Se as sodium selenite. After 100 days on these diets, the subjects began consuming 0.0, 0.5, 5.0, or 15 ppm of Hg as methylmercuric chloride in their drinking water for 16 months. Somatosensory sensitivity, grip strength, hind-limb cross (clasping reflex), flexion, and voluntary wheel-running in overnight sessions were among the measures examined. MeHg caused a dose-and time-dependent impairment in all measures, No effects appeared in rats consuming 0 or 0.5 ppm of Hg. Somatosensory function, grip strength, and flexion were among the earliest signs of exposure. Selenium significantly delayed or blunted MeHgs effects. Selenium also increased running in unexposed animals as they aged, a novel finding that may have important clinical implications. Nerve pathology studies revealed axonal atrophy or mild degeneration in peripheral nerve fibers, which is consistent with abnormal sensorimotor function in chronic MeHg neurotoxicity. Lidocaine challenge reproduced the somatosensory deficits but not hind-limb cross or flexion. Together, these results quantify the neurotoxicity of long-term MeHg exposure, support the safety and efficacy of Se in ameliorating MeHg's neurotoxicity, and demonstrate the potential benefits of Se during aging.

show abstract

Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dietary selenium protects against selected signs of aging and methylmercury exposure

et al. 2010

View full text Add to dashboard Cite

show abstract

“…90 rat pups from 16 litters were randomly assigned to three groups: control (0.9% NaCl), low dose of MeHg (0.75mg/kg/day) and high dose of MeHg (1.5mg/kg/day). The MeHg dosages are chosen based on previous literature (Kakita et al, 2000; Shigematsu et al, 2000; Sakamoto et al, 2004) in which the selected doses for the present study did not cause any significant pathological alteration in the cerebral cortex. MeHg exposure began at postnatal day 5 (PND5).…”

Section: Methodsmentioning

confidence: 99%

In vivo methylmercury exposure induced long-lasting epileptiform activity in layer II/III neurons in cortical slices from the rat

Dasari

Yuan

2010

Toxicology Letters

View full text Add to dashboard Cite

Prenatal and postnatal methylmercury (MeHg) exposure has been shown to increase neuronal excitability and seizure susceptibility. To determine if early postnatal MeHg exposure causes a similar effect, we examined changes in field potentials in layer II/III neurons in cortical slices of rat following in vivo MeHg treatment. Rats received 0 (0.9% NaCl), 0.75 or 1.5 mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which cortical slices were prepared for field potential recordings. In slices from rats treated with vehicle, single pulse stimulation of layer IV of cortical slices induced a typical field excitatory postsynaptic potential (fEPSP) with a single spike. This type of fEPSPs was also seen in slices from rats with 15 day treatment with 0.75 or 1.5 mg/kg/day MeHg. However, 30 day treatment with either MeHg dose resulted in fEPSPs with multiple spikes (epileptiform activity) in 40% of animals examined. This epileptiform activity remained observable in 50 -60% animals in which MeHg exposure had been terminated for 30 days. However, slices from control animals still showed fEPSPs with single spike. Thus, these data suggest that postnatal MeHg exposure in vivo altered neuronal excitability and induced a long-lasting hyperexcitability in cortical neurons.

show abstract

“…72 rat pups at age PND5 from 12 litters were randomly assigned to three groups: control (0.9% NaCl), 0.75 and 1.5 mg/kg/day MeHg. The MeHg dosages were chosen based on previous literature (Kakita et al, 2000; Shigematsu et al, 2000; Sakamoto et al, 2004) in which the selected doses for the present study did not induce any significant pathological alterations in the visual cortex. Physiological saline or MeHg was injected subcutaneously (sc) beginning at PND5 and continued for 15 (PND20) or 30 consecutive days (PND35), respectively (Figure 1A).…”

Section: Methodsmentioning

confidence: 99%

Low level postnatal methylmercury exposure in vivo alters developmental forms of short-term synaptic plasticity in the visual cortex of rat

Dasari

Yuan

2009

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Methylmercury (MeHg) has been previously shown to affect neurotransmitter release. Short-term synaptic plasticity (STP) is primarily related to changes in the probability of neurotransmitter release. To determine if MeHg affects STP development, we examined STP forms in the visual cortex of rat following in vivo MeHg exposure. Neonatal rats received 0 (0.9% NaCl), 0.75 or 1.5 mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which visual cortical slices were prepared for field potential recordings. In slices prepared from rats treated with vehicle, field excitatory postsynaptic potentials (fEPSPs) evoked by paired-pulse stimulation at 20 -200 ms inter-stimulus intervals showed a depression (PPD) of the second fEPSP (fEPSP2). PPD was also seen in slices prepared from rats after 15 day treatment with 0.75 or 1.5 mg/kg/day MeHg. However, longer duration treatment (30 days) with either dose of MeHg resulted in paired-pulse facilitation (PPF) of fEPSP2 in the majority of slices examined. PPF remained observable in slices prepared from animals in which MeHg exposure had been terminated for 30 days after completion of the initial 30 day MeHg treatment, whereas slices from control animals still showed PPD. MeHg did not cause any frequency-or region-preferential effect on STP. Manipulations of [Ca 2+ ] e or application of the GABA A receptor antagonist bicuculline could alter the strength and polarity of MeHg-induced changes in STP. Thus, these data suggest that low level postnatal MeHg exposure interferes with the developmental transformation of STP in the visual cortex, which is a long-lasting effect. KeywordsMethylmercury; extracellular microelectrode recording; synaptic transmission; short-term synaptic plasticity; visual cortical slice of rat

show abstract

Chronic effects of methylmercury on the cerebral function in rats

Cited by 8 publications

References 25 publications

Dietary selenium protects against selected signs of aging and methylmercury exposure

Dietary selenium protects against selected signs of aging and methylmercury exposure

In vivo methylmercury exposure induced long-lasting epileptiform activity in layer II/III neurons in cortical slices from the rat

Low level postnatal methylmercury exposure in vivo alters developmental forms of short-term synaptic plasticity in the visual cortex of rat

Contact Info

Product

Resources

About