Figure 5

Schematic drawing of the different role for MyD88 in the loss of dopaminergic neurons in the ENS vs. CNS following subacute MPTP challenge. In the ENS, MPTP induces an immune response characterized by neutrophile and monocyte infiltration, and by a pro-inflammatory immunophenotype of resident macrophages. This immune response is accompanied by dopaminergic neuronal death. Depletion of MyD88 prevents macrophage infiltration and in fact promotes a shift to pro-repair immunophenotype in monocyte population of the ENS in response to MPTP. This favorably impacts the survival of the dopaminergic neurons in the myenteric plexus. In the brain of the same mice, however, dopaminergic neurons of the substantia nigra, along with striatal terminals, undergo degeneration/depletion when exposed to MPTP. These contrasting findings may relate to the type and intensity of the inflammatory responses provoked by MPTP in the two nervous systems. Another likely scenario relates to the BBB. Unlike in the ENS [55], cell infiltration from the blood to the brain may not occur following a subacute MPTP challenge. Abbreviation: SN: substantia nigra.