FosB and ΔFosB expression in brain regions containing differentially susceptible dopamine neurons following acute neurotoxicant exposure.

Parkinson disease (PD) is characterized by progressive neuronal degeneration, in particular nigrostriatal dopamine (NSDA) neurons and consequent deficits in movement. In mice and non-human primates, NSDA neurons preferentially degenerate following exposure to the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Tuberoinfundibular (TI) DA neurons, in contrast, appear to be unaffected in PD and recover following acute MPTP exposure-induced injury (Behrouz et al., 2007; Benskey et al., 2012). The recovery of the TIDA neurons is dependent on de novo protein synthesis and positively correlated with an increase in parkin mRNA and protein expression (Benskey et al., 2012, 2015). Inhibition of parkin upregulation renders TIDA neurons susceptible to degeneration following MPTP exposure. In addition to parkin, other potentially protective proteins are likely to be differentially regulated in TIDA and NSDA neurons following neurotoxicant exposure. The regulation of potential transcription factors for parkin and other neuroprotective pathway genes are of interest since they may provide novel targets for PD disease modifying therapies. As such, we sought to determine if there are time-dependent differences in the expression of AP-1 transcription factors c-Fos, c-Jun, FosB, ΔFosB and JunD in TIDA and NSDA neurons of mice following acute MPTP exposure. We observed that both FosB and ΔFosB expression increase in brain regions containing TIDA, but not NSDA neurons. Furthermore, the nuclear and long-term expression of ΔFosB is consistent with its role as a transcription factor that may influence parkin transcription, which may underlie the unique ability of TIDA neurons to recovery from an injury that leads NSDA neurons to degeneration.