Calpastatin gene is not associated with late onset sporadic Parkinson' s disease in Chinese Han population / 中华行为医学与脑科学杂志

Objective To explore the association between late-onset sporadic Parkinson' s disease (PD) and single nucleotide polymorphisms (SNPs) of Ca2+-dependent protease calpain inhibitor calpastatin (CAST) gene in a Chinese Han population.Methods 370 evaluable patients (221 male,149 female) with PD (mean age 65.2 ± 8.5 years) and 390 neurologically healthy controls (208 male,182 female) matched for gender,ethnicity,and area of residence.PD cases were identified from the PD cohort of the Chinese National Consortium on Neurodegenerative Diseases (www.chinapd.cn).A total of 24 tag-SNPs were genotyped capturing 95％ of the genetic variation across the CAST gene.Results There was no association found between any of the polymorphisms and PD in all models tested (co-dominant,dominant-effect and recessive-effect (P ＞ 0.05)).Similarly,none of the common haplotypes was associated with a risk for PD(P ＞ 0.05).Conclusion Results show no significant association between the CAST gene polymorphisms and late onset sporadic PD in the present population.

Expression of clock genes Bmall and Bmal2 in total leukocytes in health and Parkinson's disease / 中华行为医学与脑科学杂志

Objective To study the expression of clock genes in Parkinson's disease(PD) and also the molecular clock machinery of PD.Methods Seventeen PD patients(nine men,eight women)and sixteen agematched controls(nine men,seven women) were investigated in this study.Bload samples were collected over a 12h span at 21:00,00:00,06:00 and 09:00.Using a real-time PCR assay,the peripheral molecular clock was examined by measuring Bmall and Bmal2 expression in total leukocytes during the dark span(from 21:00 to 09:00)in PD patients and age-matched healthy controls.Results At PD,the relative abundance of Bmall was significantly lower at 21:00,00:00 and 06:00(21:00:(22.17±4.09)vs(51.14±8.31),P=0.003,00:00:(30.30±5.45)vs(100.00±24.71),P=0.008,06:00:(19.02±3.33)vs(65.61±14.11),P=0.002).The relative Bmal2 levels in PD patients were significantly less abundant than controls at 21:00 and 00:00(21:00:(48.09±7.40)vs(84.96±9.34),P=0.005;00:00:((65.85±7.88)vs(100.00±11.78),P=0.025).Conclusion These results suggest that a peripheral molecular clock is altered in PD patients.In addition,the relative abundance of Bmall and Bmal2 was significantly lower in PD patients versus control subjects,which can provide a molecular basis to help monitor disease progression and response to investigational drugs.

Suprachiasmatic nucleus slices induce molecular oscillations in fibroblasts / 中华行为医学与脑科学杂志

Objective To study whether suprachiasmatic nucleus (SCN) slices are able to induce the molecular oscillations in NIH/3T3 fibroblast. Methods SCN slices from 10-day-old SD rat and NIH/3T3 cells were co-cultured in a serum-free condition. 24h mRNA profiles of Per1 and Rev-Erbα were measured in NIH/3T3 cells using real-time PCR. Results After co-cultured for 6 days, ten SCN slices can induce the significant daily oscillation of Per1 and Rev-Erba mRNA expression in NIH/3T3 cells (P<0.01). The peak time Rev-erbα and Per1 were at CT5 and CT11 respectively. Rev-Erbα oscillations were significant even with two SCN slices and 2 days co-culture (P<0.05). In contrast, Per1 expression fluctuation was not observed until more than 6 days of co-culture and with six SCN slices (P=0.031). Conclusion Diffusible signals release from SCN slices can regulate molecular rhythms in cultured fibroblasts. Rev-Erbα and Per1 don't start to oscillate at the same time, and Rev-Erbα is more sensitive to SCN signal.