Exercise elevates dopamine D2 receptor in a mouse model of Parkinson's disease: In vivo imaging with [18F]fallypride

Using Western immunoblotting analysis of synaptoneurosomes and in vivo positron emission tomography imaging employing the dopamine D2 receptor specific ligand fallypride, we found that high intensity treadmill exercise led to an increase in striatal DA-D2R expression that was most pronounced in MPTP compared to saline treated mice

Marta G. Vučcković; Quanzheng Li; Beth Fisher; Angelo Nacca; Richard M. Leahy; John P. Walsh; Jogesh Mukherjee; Celia Williams; Michael W. Jakowec; Giselle M. Petzinger


Scholarcy highlights

  • The purpose of the current study was to examine changes in dopamine D2 receptor expression within the basal ganglia of MPTP mice subjected to intensive treadmill exercise
  • This study demonstrates that high-intensity treadmill exercise leads to an increase infallypride binding potential in the striatum of MPTP treated mice
  • As DA-D2Rs are the predominant dopamine receptor subtype within dorsal striatum, an exercise-induced increase infallypride BP represents an increase in DA-D2R number and is supported by an increase in protein expression using Western immunoblotting and our previous studies showing an increase in striatal DA-D2R mRNA transcript expression using in situ hybridization histochemistry
  • This interpretation of BP elevation is further supported by the fact that displacement offallypride by dopamine is not likely to occur in MPTP mice as dopamine levels remain low
  • The enhanced effect of exercise in MPTP mice may reflect an attempt of the injured brain to optimize dopaminergic neurotransmission through increased receptor number while dopamine levels remain depleted
  • The fact that dopamine levels do not change significantly with exercise in MPTP mice suggests that compensatory changes in DA-D2R are critical for exercise related improved motor performance
  • Glutamatergic neurotransmission is enhanced through DA-D1Rs and diminished through dopamine D2 receptor. Under conditions of dopamine depletion, spines and synaptic connections are selectively lost on DA-D2R containing medium spiny neurons of the indirect pathway. This loss is accompanied with a hyperexcitability state within the MSNs due to increased glutamatergic corticostriatal neurotransmission. In animal models of Parkinson’s Disease, this increased glutamatergic drive correlates with parkinsonian-like motor behavior. Attenuation of this hyperexcitable state through the application of dopamine or its agonists leads to reversal of parkinsonian motor deficits. In light of these reports and our findings, we hypothesize that the benefits of high-intensity exercise are to enhance dopaminergic signaling through increased DA-D2R expression in the indirect pathway and to improve motor function through suppression of glutamatergic excitability

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