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.