Abnormal resting-state functional connectivity in posterior cingulate cortex of Parkinson's disease with mild cognitive impairment and dementia.

OBJECTIVE: To investigate changes in the functional connectivity (FC) pattern in the posterior cingulate cortex (PCC) of Parkinson's disease (PD) patients with mild cognitive impairment and dementia by employing resting-state functional magnetic resonance imaging (RS-fMRI). METHODS: Twenty-seven PD patients with different cognitive status and 9 healthy control subjects (control group) were enrolled for RS-fMRI. The RS-fMRI data were analyzed with DPARSF and REST software. Regions with changed functional connectivity were determined by the seed-based voxelwise method and compared between groups. Correlation between the intensity of FC and the MoCA scores of PD group was analyzed. RESULTS: Parametric maps showed statistical increases in PCC functional connectivity in PD-MCI patients and decreases in PCC connectivity in PDD patients. The latter group of patients also showed evidence for increased connectivity between prefrontal cortices and posterior cerebellum. A significant positive correlation was found between the MoCA scores and the strength of PCC connectivity in the angular gyrus and posterior cerebellum and a negative correlation between MoCA scores and PCC connectivity in all other brain regions. CONCLUSION: When patients transition from PD-NCI to PD-MCI, there appears to be an increase in functional connectivity in the PCC, suggesting an expansion of the cortical network. Another new network (a compensatory prefrontal cortical-cerebellar loop) later develops during the transition from PD-MCI to PDD.

Long noncoding RNA MALAT1 inhibits apoptosis induced by oxygen-glucose deprivation and reoxygenation in human brain microvascular endothelial cells.

Cerebral ischemia/reperfusion (I/R) injury leads to brain vascular dysfunction, which is characterized by endothelial cell injury or death. Long noncoding (lnc) RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is reportedly associated with endothelial cell functions and dysfunctions. In the present study, the role of MALAT1 in I/R-induced cerebral vascular endothelial cell apoptosis was explored using oxygen-glucose deprivation and reoxygenation (OGD-R) as an in vitro I/R injury model. Primary human brain microvascular endothelial cells were cultured under OGD-R, and the expression levels of MALAT1 and cell apoptosis were measured at 6, 9, 12, 24 and 36 h post-reoxygenation. The expression levels of MALAT1 and the apoptotic rate of cells exposed to OGD-R exhibited contrasting trends following reoxygenation. Following OGD-R, lentiviral overexpression of MALAT1 increased phosphatidylinositol 3-kinase (PI3K) activities and the activation of Akt phosphorylation, and decreased cell apoptosis and caspase 3 activities, which were successfully abolished by treatment with a PI3K inhibitor, Wortmannin. Conversely, lentiviral knockdown of MALAT1 decreased PI3K activities and the activation of Akt phosphorylation, and increased cell apoptosis and caspase 3 activity. Overexpression and knockdown of MALAT1 exhibited no significant effects on OGD-R-induced reactive oxygen species (ROS) production. In conclusion, to the best of our knowledge, the present study was the first to suggest that lncRNA MALAT1 may protect human brain vascular endothelial cells from OGD-R-induced apoptosis via a PI3K-dependent mechanism. These findings suggest that MALAT1 may be a potential novel therapeutic target for cerebral I/R injury.

[Association of estrogen receptor ß gene polymorphisms with hypertension in postmenopausal women].

OBJECTIVE: To explore the association between estrogen receptor ß (ERß) gene polymorphisms and hypertension in postmenopausal women. METHODS: The relationship of two polymorphisms (rs944050 and rs4986938) with hypertension was examined in 71 postmenopausal women with hypertension and 50 healthy age-matched controls. RESULTS: In hypertension and control groups, the ERß allelic frequencies of A and G were 0.500, 0.500, 0.540, 0.460; 0.077, 0.923, 0.170, 0.830 respectively. The genotypic distributions of both polymorphisms stayed within Hardy-Weinberg equilibrium. For polymorphism rs4986938, statistical difference existed between the wild-type genotype and a combination of heterozygous and homozygous variant genotypes (P < 0.05). The variant allele A of rs4986938 in ERß gene decreased the risk of hypertension (OR = 0.41, 95%CI 0.18-0.92). CONCLUSION: The polymorphism rs4986938 in ERß gene was associated with an elevated risk of hypertension in Chinese Han postmenopausal women.