Junji Wakamiya

Involvement of enhanced sensitivity of N-methyl-d-aspartate receptors in vulnerability of developing cortical neurons to methylmercury neurotoxicity

The developing cortical neurons have been well documented to be extremely vulnerable to the toxic effect of methylmercury (MeHg). In the present study, a possible involvement of N-methyl-D-aspartate (NMDA) receptors in MeHg neurotoxicity was examined because the sensitivity of cortical neurons to NMDA neurotoxicity has a similar developmental profile. Rats on postnatal day 2 (P2), P16, and P60 were orally administered MeHg (10 mg/kg) for 7 consecutive days. The most severe neuronal damage was observed in the occipital cortex of P16 rats. When MK-801 (0.1 mg/kg), a non-competitive antagonist of NMDA, was administered intraperitoneally with MeHg, MeHg-induced neurodegeneration was markedly ameliorated. Furthermore, there was a marked accumulation of nitrotyrosine, a reaction product of peroxynitrite and L-tyrosine, after chronic treatment of MeHg in the occipital cortex of P16 rats. The accumulation of nitrotyrosine was also significantly suppressed by MK-801. In the present electrophysiological study, the amplitude of synaptic responses mediated by NMDA receptors recorded in cortical neurons of P16 rats was significantly larger than those from P2 and P60 rats. These observations strongly suggest that a generation of peroxynitrite through activation of NMDA receptors is a major causal factor for MeHg neurotoxicity in the developing cortical neurons. Furthermore, enhanced sensitivity of NMDA receptors may make the cortical neurons of P16 rats most susceptible to MeHg neurotoxicity.

An epidemiological study with risk analysis of liver diseases in the general population living in a methyl mercury polluted area.

STUDY OBJECTIVE--The aim was to determine the actual prevalence of liver disease and to investigate the contribution of various risk factors to liver disease among the population in a methyl mercury polluted area. DESIGN--The study was a population based cross sectional mass screening survey. A case-control study was designed to estimate the role of various risk factors for liver diseases. SETTING--The study was confined to a small rural town 10 km north of Minamata City. SUBJECTS--1406 persons aged 50 to 69 years were examined (78.3% of the total population of this age in the locality). MEASUREMENTS AND MAIN RESULTS--Measurements of liver disease were made on the basis of haematological, physical, and ultrasonographic examinations. Data on liver risk factors were collected by questionnaire, and by measurement of body height, weight (obesity), and hepatitis B surface antigen (HBsAg). The prevalence rate of liver tumour was 0.5% in males, liver cirrhosis was found in 0.5% of males and 0.1% of females, and hepatitis was seen in 5.4% of males and 1.0% of females. Frequency rates of risk factors for liver disease among subjects with obesity were significantly higher in the female patient group, and the frequency rate among subjects with alcoholic drinking habits was significantly higher in the male patient group. The odds ratio of past history of blood transfusion showed the highest value among other related factors (7.73) and the attributable risk for this was very high (87.1%); HBsAg was next in rank (odds ratio 3.04; attributable risk 67.1%). CONCLUSIONS--The prevalence of liver disease in this methyl mercury polluted area was not increased, contrary to what was expected based on the standard mortality ratios. The main risk factors for liver disease in this area appear to be alcoholic drinking habits and a history of blood transfusion.

Serial study on the association between body mass index and hypertension in rural Japanese.

The objective of this study was to examine the association between body mass index (BMI) and blood pressure. Two sets of cross-sectional data were obtained from annual health examinations for adults aged 40 years and over (n=1,327 in 1993; n=1,302 in 2000) in Tsunagi area of Kumamoto Prefecture, Japan. BMI was associated with mean blood pressure and with prevalence of hypertension both in 1993 and 2000. The association was independent of age, smoking status and alcohol consumption. A significant increase in risk of hypertension was found in most categories of BMI 25.0 and above, and a greater than three fold increase in those with BMI of 27 and above compared with those with BMI of 18.5–22.9. Although mean blood pressure and prevalence of hypertension sharply decreased in 2000 compared with that in 1993, BMI was positively and independently associated with increased blood pressure.

Protective effect of MK-801 in methyl mercury induced neuronal injury

KEN-ICHIRO MIYAMOTO’.KOJI MURAO’,JUNJI WAKAMIYA’,KOMYO ETO’. MINESHI SAKAMOTO’ KIMIYOSHI ARIMURA”, MITSUHIRO OSAME’ ‘National Institute for Minamata Disease, Minamata ,Kumamoto, 867-0008, *Third Dept. of Internal medicine, Kagoshima Univ.,Kagoshima. 890-0075 We Studied in vivo experimental systems whether glutamate and glutamate receptors are involved in the onset of neurotoxicity mechanisms of brain neuronal damage in methyl mercury administered neonatal rat. Male \Vistar rats were used 16 days after birth. We separated them to six experimental groups: Control group(grou A), MK-801 0.1 mglkgiday for 7 days i.p. alone(group B). AMPAikainate receptors antagonist YM SOK 15 mglkgiday for 7 days i.p. alone (group C), MMC 10 mgikgiday + condensed milk + equimolar of systein for 7 days p,o. alone (group D ), MMC+MK-80l(group E), MMC+YMSOK(grou F). Group D showed the neuronal damage of cerebral cortex. MK-801 reduced the neuronal damage of cerebral cortex, but YMSOK did not reduce. These results were indicated that excitotoxic amino acids are involved in the MMC induced neuronal injury.