Loss of Corticostriatal Mu-Opioid Receptors in α-Synuclein Transgenic Mouse Brains

Jessica Grigoletto, Meir Schechter, Ronit Sharon

Research output: Contribution to journalArticlepeer-review

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 corticos-triatal 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.

Original languageAmerican English
Article number63
JournalLife
Volume12
Issue number1
DOIs
StatePublished - 3 Jan 2022

Keywords

  • Corticostriatal glutamatergic axons
  • Mu-opioid receptors (MOR)
  • White matter tracts (WMTs)
  • α-Synuclein

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Palaeontology
  • Space and Planetary Science

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