Serum antibodies from Parkinson's disease patients react with neuronal membrane proteins from a mouse dopaminergic cell line and affect its dopamine expression

Evidence exists suggesting that the immune system may contribute to the severity of idiopathic Parkinson's disease (IPD). The data presented here demonstrates that antibodies in the sera of patients with IPD have increased binding affinity to dopaminergic (DA) neuronal (MN9D cell line) membrane antigens in comparison to antibodies in sera from healthy controls. In general, the degree of antibody reactivity to these antigens of the mouse MN9D cell line appears to correlate well with the disease severity of the IPD patients contributing sera, based on the total UPDRS scores. Surprisingly, the sera from IPD patients enhanced the DA content of MN9D cells differentiated with n-butyrate; the n-butyrate-differentiated MN9D cells had a greater concentration of DA (DA/mg total protein) than undifferentiated MN9D cells, especially early in culture. Although the IPD sera did not directly harm MN9D cellular viability or DA production, in the presence of the N9 microglial cell line, the amount of DA present in cultures of untreated or n-butyrate-treated MN9D cells was lowered by the IPD sera. The results suggest the involvement of antibodies in the decline of dopamine production and, thus, the potential of immune system participation in IPD

Neurotoxicity of polychlorinated biphenyls and related organohalogens.

Halogenated organic compounds are pervasive in natural and built environments. Despite restrictions on the production of many of these compounds in most parts of the world through the Stockholm Convention on Persistent Organic Pollutants (POPs), many "legacy" compounds, including polychlorinated biphenyls (PCBs), are routinely detected in human tissues where they continue to pose significant health risks to highly exposed and susceptible populations. A major concern is developmental neurotoxicity, although impacts on neurodegenerative outcomes have also been noted. Here, we review human studies of prenatal and adult exposures to PCBs and describe the state of knowledge regarding outcomes across domains related to cognition (e.g., IQ, language, memory, learning), attention, behavioral regulation and executive function, and social behavior, including traits related to attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). We also review current understanding of molecular mechanisms underpinning these associations, with a focus on dopaminergic neurotransmission, thyroid hormone disruption, calcium dyshomeostasis, and oxidative stress. Finally, we briefly consider contemporary sources of organohalogens that may pose human health risks via mechanisms of neurotoxicity common to those ascribed to PCBs