6-Hydroxydopamine as a tool to understand adaptive immune system-induced dopamine neurodegeneration in Parkinson's disease

Abstract

Context: Neuroimmunological response is associated with neurodegeneration in the human substantia nigra (SN) in Parkinson’s disease (PD).

Objective: To explore the possibility that the neurotoxin, 6-hydroxydopamine (6-OHDA), could be used as a tool in mice to understand the immune response in PD.

Materials and methods: We employed unilateral administration of 6-OHDA into the mouse SN. At 1 week, 2 weeks and 4 weeks post-injection, we used immunohistochemistry for the markers Iba-1 and gp91PHOX to investigate activated microglia in the SN. To examine the adaptive immune response, we used immunohistochemistry for CD3-positive T-lymphocytes, CD45R-positive B-lymphocytes and anti-mouse immunoglobulin-G (IgG). Dopamine neuron loss was examined using immunohistochemistry for the dopamine neuron marker, tyrosine hydroxylase.

Results: Compared to vehicle, 6-OHDA administration induced an intense IgG deposition in the SN as well as increased infiltration of both T- and B- lymphocytes into the injected side of the midbrain. The adaptive immune response was associated with extensive destruction of dopamine neurons and extensive microglial activation at every time point in the 6-OHDA groups.

Conclusion: Our results suggest that 6-OHDA administration in mice can a potential tool for understanding mechanisms underlying adaptive immune activation-induced neurodegeneration in PD.

• Glia
• immunoglobulins
• lymphocytes
• neuroimmunology
• neurotoxin

Acknowledgments

The authors thank the McGuire Research Institute and the VA Animal Care Facility for their help and guidance in this study.

Declaration of interest

The authors have no declarations of interest to report. This work was supported by funding from the Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia and VA Merit Review Award BX001131 to WFM.