Effect of stress on neuroinflammation in the substantia nigra and striatum of LRRK2 (R1441G) mouse model for Parkinson’s disease

Abstract

Stress is known to have a pro-inflammatory effect on the CNS. Neuroinflammation mediated by microglia activation and proliferation in the substantia nigra and striatum may play a significant role in PD progression. Our objective in this project was to investigate the effect of stress on neuroinflammation in the LRRK2 (R1441G) mouse model for Parkinson’s disease. Mice carrying the R1441G mutant of the human LRRK2 gene were challenged with neurotoxins and environmental stress. Results showed that microglia may be increased in stressed mice by immunostaining with CD11b and proliferative cells were present by immunostaining with Ki-67, but could not be linked to microglial proliferation. Further quantification is required to confirm these observations. The onset of neuroinflammation was found to occur before appearance of motor deficits. In addition, the inclusion of another experimental group, mice challenged with environmental stress but not neurotoxins, allowed the analysis of the effect of chronic stress on the genotype and neurotoxins. Neurotoxins appeared to make mice more susceptible to stress, but a greater sample size is needed for significance.