Sporadic neurodegenerative diseases would have well-documented environmental causes.Neurodegeneration often accompanies with inflammation. Brain inflammation is a complex cellular and molecular response to stress, injury or infection of the central nervous system to defend against insults, clear dead and damaged neurons and return the central nervous system to a normal state. Inflammation in the brain is driven by the activation of resident microglia, astrocytes and infiltrating peripheral macrophages, which release a plethora of anti- and proinflammatory cytokines, chemokines, neurotransmitters and reactive oxygen species.
There are several lines of evidence to suggest that neuroinflammation plays a role in the degeneration of dopaminergic neurons in Parkinson's disease.In this study, an animal model of Parkinson's disease was developed with exposure of adult rats to environmental chemicals such as rotenone and p-nitrotoluene with osmotic pumps and examined the dynamics of cytokine proteins as well as gene expression.
Environmnetal chemicals (3 mg/kg/day) were subcutaneously infused to male Wistar rats at 7-9 weeks of age, using Alzet minipumps. Exposure of adult rat to chemicals caused muscular rigidity, poor balance, and problems in gait. The spontaneous motor activity was 10-49% less than that of control rat. At 11 weeks old, rat brains were subjected to Bioplex analysis for measurement of cytokine amounts and to gene expression analysis.
Gene expression profiles showed the good corretion between those with rotenone and p-nitrotoluene. Gene set enrichment analyses suggested that rotenone would influence the cytokine networks. As predicted by the network analyses with gene expression, the amount of TNF-alpha was decreased 45.4%, whereas the levels of cytokine proteins such as IL-2, IL-4, IL-6, IL-10, IL-17, and IL-18 tended to decrease with no statistical significance. However, chronic exposure to p-nitorotoluene for 28 days significantly decreased the levels of all cytokines tested (p< 0.05).
Thus, neurodegeneration accompanies with the dynamics of cytokine proteins in environmenta chemical models of Parkinson's disease as seen in the patients.