Brain iron levels in patients of Parkinson’s disease (PD) are usually measured in postmortem samples or by MRI imaging including R2* and SWI. In this study we performed a meta-analysis to understand PD-associated iron changes in various brain regions, and to evaluate the accuracy of MRI detections comparing with postmortem results. Databases including Medline, Web of Science, CENTRAL and Embase were searched up to 19th November 2015. Ten brain regions were identified for analysis based on data extracted from thirty-three-articles. An increase in iron levels in substantia nigra of PD patients by postmortem, R2* or SWI measurements was observed. The postmortem and SWI measurements also suggested significant iron accumulation in putamen. Increased iron deposition was found in red nucleus as determined by both R2* and SWI, whereas no data were available in postmortem samples. Based on SWI, iron levels were increased significantly in the nucleus caudatus and globus pallidus. Of note, the analysis might be biased towards advanced disease and that the precise stage at which regions become involved could not be ascertained. Our analysis provides an overview of iron deposition in multiple brain regions of PD patients, and a comparison of outcomes from different methods detecting levels of iron.

Background: Paroxetine, a selective serotonin reuptake inhibitor for counteracting depression, has been recently suggested as having a role in prevention of dopaminergic neuronal degeneration in substantia nigra, a hallmark of Parkinson's disease (PD). The pathogenesis of this type of neurological disorders often involves the activation of microglia and associated inflammatory processes. Thus in this study we aimed to understand the role of paroxetine in microglia activation and to elucidate the underlying mechanism(s). Methods: BV2 and primary microglial cells were pretreated with paroxetine and stimulated with lipopolysaccharide (LPS). Cells were assessed for the responses of pro-inflammatory mediator and cytokines, and the related signaling pathways were evaluated and analyzed in BV2 cells. Results: Paroxetine significantly inhibited LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α and IL-1β. Further analysis showed inducible nitric oxide synthase (iNOS) and mRNA expression of TNF-α and IL-1β were attenuated by paroxetine pretreatment. Analyses in signaling pathways demonstrated that paroxetine led to suppression of LPS-induced JNK1/2 activation and baseline ERK1/2 activity, but had little effect on the activation of p38 and p65/NF-κB. Interference with specific inhibitors revealed that paroxetine-mediated suppression of NO production was via JNK1/2 pathway while the cytokine suppression was via both JNK1/2 and ERK1/2 pathways. Furthermore, conditioned media culture showed that paroxetine suppressed the microglia-mediated neurotoxicity.

It has been recently proposed by a genome-wide association study (GWAS) meta-analysis that the CCDC62 variant rs12817488 is a new risk locus associated with Parkinson's disease (PD). In this study, we aimed to investigate the association between rs12817488 and PD in a Chinese cohort. A total of 341 PD patients and 423 matched controls were recruited in Eastern China. Our results showed that the A allele of rs12817488 was significantly associated with an aggravated risk of PD (p = 0.006) and represented a major allele in contrast to a minor one in Caucasians. Genotype distributions also differed between PD patients and controls (p = 0.011 for AA/AG/GG). Further analysis showed that the association of rs12817488 with PD only existed in females. We also investigated the protein level of CCDC62 in peripheral blood mononuclear cells from 41 AA or GG carriers and found an apparently higher expression in PD patients carrying the AA genotype. A potential interaction was found between two estrogen-related loci, i.e. rs12817488/CCDC62 and rs2697962/PRDM2, particularly in the female stratum. In conclusion, our study demonstrated for the first time a significant association between the rs12817488 polymorphism and PD predisposition in a Chinese population with gender variations and provides new insight regarding the variant's protein expression and estrogen-related genetic interaction.

Background: Few studies have compared the etiology and clinical features between pure lateral medullary infarction (LMI) and pure medial medullary infarction (MMI).

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