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Background: Moyamoya disease-an idiopathic vascular disorder of intracranial arteries-is often accompanied by hypertension. RNF213 has been identified as a susceptibility gene for moyamoya disease. In the present study, the association of p.R4810K (G>A) with blood pressure (BP) was investigated in a Japanese population. Methodology/principal findings: Three independent study populations, the Nyukawa ( n = 984), Noshiro ( n = 2,443) and Field ( n = 881) studies, joined this study. BP, body weight and height were measured. Past and present symptoms and disease and medication histories were assessed by interview. Associations of p.R4810K (rs112735431, ss179362673) of RNF213 with BP were investigated. Two linkage disequilibrium blocks were constructed for moyamoya patients with p.R4810K ( n = 140) and the general population ( n = 384) using 39 single nucleotide polymorphisms (SNPs) spanning 390 kb around RNF213. A total of 60 carriers (3 for AA genotype and 57 for GA genotype) were found in these samples, and the minor allele frequencies were 1.4 % in the Nyukawa and Field studies and 0.2 % in the Noshiro study. Regression analyses adjusted for age, sex and body mass index based on an additive model demonstrated significant associations with systolic BP (mmHg/allele): β (standard error) was 8.2 (2.9) in the Nyukawa study ( P = 4.7 × 10), 18.7 (5.4) in the Noshiro study ( P = 4.6 × 10) and 8.9 (2.0) ( P = 1.0 × 10) in the three populations. In contrast, diastolic BP showed significant associations only in the Noshiro study. Linkage disequilibrium blocks contained none of the BP-associated proxy SNPs reported by previous studies. Conclusions/significance: Our study suggests that p.R4810K of RNF213 is associated strongly with systolic BP. [ABSTRACT FROM AUTHOR]

To investigate the mechanism by which developmental iodine deficiency and hypothyroidism affect long-term synaptic plasticity, we chose to study the activity of protein kinase C (PKC) and the expression of growth-associated protein-43 (GAP-43) in pup hippocampus following developmental hypothyroidism. Two developmental hypothyroid rat models were created with iodine-deficient diet (IDD) and water containing methimazole. Compared to the control group, in developmental hypothyroid rats: (i) HFS induced less in vivo LTP and more long-term depression (LTD) in area CA1 on postnatal day (PN) 60 (P < 0.0 5); (ii) in IDD pups, HFS-induced LTP showed much smaller population spike amplitude (P < 0.01) and slope of field-excitatory postsynaptic potential (P < 0.01); (iii) PKC activity, on PN30, was much higher on cell membrane and lower in cytosol (P < 0.05) without change of total PKC level (P > 0.05); and (iv) GAP-43 expression was significantly lower (P < 0.01) on both PN30 and PN60. Developmental iodine deficiency and hypothyroidism affect PKC translocation, decrease GAP-43 expression, and impair long-term synaptic plasticity in the rat hippocampus. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect of iodine deficiency and hypothyroidism on the expression of extracellular signal-regulated protein kinase 1/2 (ERK1/2) in the hippocampus of rat pups., Methods: Pregnant Wistar rats (n=28) were randomly divided into control group, hypothyroid group (containing PTU 5 mg/L and 15 mg/L in drinking water) and iodine deficient group. The brains of 5 pups from each group were fixed by intracardiac perfusion at 7, 14, 21, 28 and 42 days after birth. Brain sections were observed and analyzed by immunohistochemistry on the expression of ERK1/2 in the CA1, CA3 and DG regions of hippocampus., Results: The expressions of ERKl/2 in CA1 and CA3 regions of hippocampus in iodine-deficient group, PTU 5 mg/L group and PTU 15 mg/L group were significantly lower than those in control group (P < 0.05) at 14, 21, 28 and 42 days after birth. The expression of ERK1/2 in DG region was not significantly different in all four groups. The expressions of ERK1/2 were not significantly different in all four groups at 7 days after birth., Conclusion: Iodine deficiency and hypothyroidism may decrease the expression of ERK1/2 in the hippocampus of pups.

Objective: To observe the effect of iodine deficiency and hypothyroidism on the protein expressions of CaMK II in the hippocampus of pups., Methods: Female Wistar rats (n=28) after pregnancy were randomly divided into control group, hypothyroid group and iodine deficient group. According to the dose of PTU in fed water, hypothyroid group was divided into 5 mg/L group and 15 mg/L group (7 in each). 5 pups from each group were sacrificed and perfused intracardially in PN7, PN14 and PN21. Brains were removed, fixed and sectioned coronally. All sections were observed and analyzed the protein exression of CaMK II by immunohistochemistry in the hippocampus CA1, CA3 and DG regions., Results: Control group in CA1, CA3 and DG regions of the hippocampus had strong positive staining and the cytoplasm of neurons were filled with CaMK II. The distribution of the immune reaction product in hippocampus of 5 mg/L, 15 mg/L and iodine groups were in line with the control group, but the staining intensity as compared with the control group gradually decreased. In PN21 and PN14, integrated optical density average of CaMK II in CA1, CA3 and DG regions of the hippocampus in iodine deficient group [PN21: (26.05 +/- 4.98), (30.79 +/- 3.22), (26.40 +/- 2.63); PN14:(25.48 +/- 4.87), (44.17 +/- 5.91), (26.41 +/- 3.01)] and 15 mg/L groups [PN21: (17.02 +/- 2.68), (24.57 +/- 6.62), (20.18 +/- 4.05); PN14:(20.66 +/- 3.51), (34.94 +/- 5.09), (27.32 +/- 4.97)] were significantly lower than those of controls [PN21: (57.75 +/- 13.22), (65.03 +/- 6.20), (49.39 +/- 8.41), P < 0.05; PN14: (54.08 +/- 12.00), (71.04 +/- 5.07), (78.52 +/- 12.42), P < 0.05]. In PN7, integrated optical density average of CaMK II in CA1 region of the hippocampus in iodine deficient group (25.74 +/- 3.33) and 15 mg/L groups (26.89 +/- 5.25) were significantly lower than those of controls(40.53 +/- 3.65), P < 0.05., Conclusion: Iodine deficiency and hypothyroidism may decrease the protein expression of CaMK II.

Moyamoya disease (MMD) is characterized by progressive stenosis and occlusion of the terminal portion of the bilateral carotid arteries as well as arterial collateral vessels. The etiology of MMD, however, remains unknown. Several pieces of evidence suggest the involvement of genetic factors in MMD: over 10% of MMD patients have affected blood relatives; concordance in the affection status has been proven in 80% of identical twins; and there is an ethnic predisposition to MMD, the incidence of the disease being the highest in the Asian population. With regard to genetic factor (s), transmission of MMD does not follow the classic Mendelian law, i.e., skipping of a generation and discordance in identical twins, thereby indicating that genetic influence is likely to determine the susceptibility to MMD. This study aimed to overview the recent findings related to the genetic determinants in MMD and to provide research perspectives for the next decade. Pathophysiological investigations at molecular levels have uncovered the upregulation of various growth and stress response factors that are associated with angiogenesis in occlusive cerebral arteries.

This investigation aims to observe the intelligence and psychomotor development of the schoolchildren in iodine deficiency (ID) areas after the adoption of Universal Salt Iodization (USI), and evaluate the effect of the adoption of USI on their intelligence and psychomotor development. 564 schoolchildren (306 males and 258 females, age range from 8 to 13 yrs) from areas with severe, moderate, and mild ID were investigated. Intelligence quotient (IQ) was measured by Combined Raven's test, second edition. Psychomotor development was examined by Jinyi Psychomotor Test Battery (JPB). We found that the IQ scores of all subjects in the severe and moderate ID areas were 102 +/- 15.6 and 99.5 +/-16.6 respectively, lower than those in the mild ID areas (108 +/- 12.4, p < 0.01). The IQ scores correlated negatively with age (partial r = -0.17; beta = -1.95; p < 0.0001). The total T scores of JPB of all subjects in the severe and moderate ID areas were 316 +/- 42.3 and 330 +/- 47.7 respectively, lower than those in the mild ID areas (342 +/- 48.1, p < 0.05). The total T scores of JPB correlated negatively with age (partial r = -0.15; beta = -4.94; p = 0.0006). We may conclude that after the adoption of USI in the ID areas investigated, USI has probably made a contribution to the partial recovery of intelligence and psychomotor development injured by ID in schoolchildren, and should be strengthened.