Association between polychlorinated biphenyls and Parkinson's disease neuropathology

Abstract

Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson’s disease, including greater susceptibility of females.

Reduced vesicular storage of catecholamines causes progressive degeneration in the locus ceruleus

“…We observed that genetic VMAT2 deficiency in vivo drives catecholamine depletion in the central nervous system and heart and increases relative cytosolic catecholamine catabolism by MAO. These findings in transgenic mice bear particular relevance to the pathology of PD where vesicular function may be compromised as a consequence of exogenous insult (Corrigan et al, 1998; Hatcher-Martin et al, 2012), genetic polymorphism (Brighina et al, 2013; Glatt et al, 2006; Uhl et al, 2000), or a cytosolic milieu that favors an oxidative state, especially with mitochondrial dysfunction (Schapira, 2011) and aging (Cruz-Muros et al, 2008). Indeed, post-mortem analysis of putamen tissue has revealed that PD patients exhibit neurochemical indices of reduced vesicular uptake of DA and buildup of DOPAL, a toxic MAO metabolite of DA (Goldstein et al, 2013).…”

Environment, lifestyle, and Parkinson's disease: Implications for prevention in the next decade

“…Despite its removal from gasoline and most paint products, lead remains a ubiquitous environmental pollutant. Biologically plausible relationships have been suggested with other pervasive environmental exposures, such as polychlorinated biphenyls and urban air pollution, but the findings are inconsistent.…”

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

“…In a retrospective mortality study examining PCB exposure amongst workers in capacitor plants, sex-specific analyses found higher deaths from PD amongst exposed women [140]. In a case-control study examining post-mortem brain tissue from PD, AD, and control patients, PCB levels were higher in PD groups, and when stratified by age, were higher amongst women [141]. …”