Abstract
Ultrastructural, neurochemical, and molecular alterations within the striatum are associated with the onset and progression of Parkinson’s disease (PD). In PD, the dopamine-containing neurons in the substantia nigra pars compacta (SNc) degenerate and reduce dopamine-containing innervations to the striatum. The loss of striatal dopamine is associated with enhanced corticostriatal glutamatergic plasticity at the early stages of PD. However, with disease progression, the glutamatergic corticostriatal white matter tracts (WMTs) also degenerate. We analyzed the levels of Mu opioid receptors (MORs) in the corticostriatal WMTs, as a function of α-Synuclein (α-Syn) toxicity in transgenic mouse brains. Our data show an age-dependent loss of MOR expression levels in the striatum and specifically, within the caudal striatal WMTs in α-Syn tg mouse brains. The loss of MOR expression is associated with degeneration of the myelinated axons that are localized within the corticostriatal WMTs. In brains affected with late stages of PD, we detect evidence confirming the degeneration of myelinated axons within the corticostriatal WMTs. We conclude that loss of corticostriatal MOR expression is associated with degeneration of corticostriatal WMT in α-Syn tg mice, modeling PD.
Highlights
Parkinson’s disease (PD) is primarily defined as a movement disorder, the patients present non-motor and behavioral symptoms [1]
Opioid transmission in the basal ganglia has been implicated in PD [7,8,9,10] and enhanced opioid transmission is suggested to play a compensatory role in the altered basal ganglia function following depletion of striatal dopamine [8,9]
Mu opioid receptors (MORs) signal, detected within white matter tracts (WMTs) (Figure 1B,C) was normalized to the immunoreactive signal obtained for NF-200, which was found to be stable between 2–12 months of age [28] (Figure 1C,D)
Summary
Parkinson’s disease (PD) is primarily defined as a movement disorder, the patients present non-motor and behavioral symptoms [1]. Data show that loss of dopaminergic innervation to the dorsal striatum is associated with enhanced glutamatergic input to this region [3,4], suggesting that alterations in dopaminergic and glutamatergic inputs to the striatum underlie its complex dysfunction, including motor and non-motor dysfunction, during the course of the disease. Opioid transmission in the basal ganglia has been implicated in PD [7,8,9,10] and enhanced opioid transmission is suggested to play a compensatory role in the altered basal ganglia function following depletion of striatal dopamine [8,9]. Striatal MOR expression is reported to play a role in hedonic processing and reward function [11,12,13], and alterations in the availability of striatal MOR may underlie a subset of disease symptoms [5]
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