Amelioration of olfactory dysfunction in a mouse model of Parkinson's disease via enhancing GABAergic signaling.

BACKGROUND: Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson's disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown. RESULTS: We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice. CONCLUSIONS: Taken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD.

Comprehensive Assessment of the Association between FCGRs polymorphisms and the risk of systemic lupus erythematosus: Evidence from a Meta-Analysis.

We performed a meta analysis to assess the relationship of FCGRs polymorphisms with the risk of SLE. Thirty-five articles (including up to 5741 cases and 6530 controls) were recruited for meta-analysis. The strongest association was observed between FCGR2B rs1050501 and SLE under the recessive genotypic model of C allele in the overall population (CC vs CT/TT, OR = 1.754, 95%CI: 1.422-2.165, P = 1.61 × 10(-7)) and in Asian population (CC vs CT/TT, OR = 1.784, 95%CI; 1.408-2.261, P = 1.67 × 10(-6)). We also found that FCGR3A rs396991 were significant association with the susceptibility to SLE in overall population in recessive model of T allele (TT vs TG/GG, OR = 1.263, 95%CI: 1.123-1.421, P = 9.62 × 10(-5)). The results also showed that significant association between FCGR2A rs1801274 and SLE under the allelic model in the overall population (OR = 0.879 per A allele, 95%CI: 0.819-0.943, P = 3.31 × 10(-4)). The meta-analysis indicated that FCGR3B copy number polymorphism NA1·NA2 was modestly associated with SLE in overall population (OR = 0.851 per NA1, 95%CI: 0.772-0.938, P = 1.2 × 10(-3)). We concluded that FCGR2B rs1050501 C allele and FCGR3A rs396991 T allele might contribute to susceptibility and development of SLE, and were under recessive association model. While, FCGR2A rs1801274 A allele and FCGR3B NA1 were associated with SLE and reduced the risk of SLE.

Ethnicity-stratified analysis of the association between IL-18 polymorphisms and systemic lupus erythematosus in a European population: a meta-analysis.

We performed a meta-analysis to identify the association between polymorphisms in the promoter of interleukin-18 (IL-18) and susceptibility for systemic lupus erythematosus (SLE) . Genotype data for three single-nucleotide polymorphisms (SNPs rs360719, rs1946518, and rs187238) in the IL-18 promoter were extracted from 20 studies of three different ethnicities (European, Asian, and South American). Data from each ethnicity group and their combinations were analyzed. We found distinct evidence of an association between rs360719 and SLE (P = 0.001) in the European/South American group [odds ratio (OR) 1.31 per C allele, 95% confidence interval (CI) 1.11-1.53]. Stratification analysis by ethnicity showed a significant association between rs360719 and SLE in the European population (OR 1.33 per C allele, 95% CI 1.11-1.61, P = 0.003) and a lesser effect in the same direction in the South American population (OR 1.18). A significant association was also identified between rs1946518 and SLE in the European population (OR 1.16 per A allele, 95% CI 1.03-1.30, P = 0.017), although there was no association in the Asian or the combined European/Asian population. We also examined genome-wide association study (GWAS) data from an Asian subpopulation (Chinese) for the association between rs1946518 and SLE, but found no association (P = 0.83). The third SNP, rs187238, was not significantly associated with SLE in any of the populations examined. In summary, this study identified a significant association between SLE and two SNPs within the IL-18 gene promoter region (rs360719 and rs1946518) in a European population, but not in populations of Asian origin.

Simultaneous determination of Se, trace elements and major elements in Se-rich rice by dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS) after microwave digestion.

A quick and accurate method was devised to determine Se, As, Ba, Ca, Cd, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Sr and Zn in Se-rich rice samples by microwave digestion and inductively coupled plasma-mass spectrometry (ICP-MS). Spectral interferences on Se were eliminated using methane as a reaction gas in the dynamic reaction cell (DRC). Rhodium was used as an internal standard to compensate for sample matrix effects. A rice-certified reference material (CRM) (GBW 10010) was used to verify the accuracy of the method. The method detection limits were 0.001-0.03 mg/kg, analyte recoveries were 85-108% and precisions (RSDs) ranged from 2.1% to 5.8%. Correlation analysis showed that the Se concentrations in the Se-rich rice samples correlated well with the Cu concentrations (r=0.53, p<0.05).