Executive function deficits and glutamatergic protein alterations in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

Lacey Pflibsen, Katherine A. Stang, Michelle D. Sconce, Vanessa B. Wilson, Rebecca L. Hood, Charles K. Meshul, Suzanne H. Mitchell

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Changes in executive function are at the root of most cognitive problems associated with Parkinson's disease. Because dopaminergic treatment does not necessarily alleviate deficits in executive function, it has been hypothesized that dysfunction of neurotransmitters/systems other than dopamine (DA) may be associated with this decrease in cognitive function. We have reported decreases in motor function and dopaminergic/glutamatergic biomarkers in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinson's mouse model. Assessment of executive function and dopaminergic/glutamatergic biomarkers within the limbic circuit has not previously been explored in our model. Our results show progressive behavioral decline in a cued response task (a rodent model for frontal cortex cognitive function) with increasing weekly doses of MPTP. Although within the dorsolateral (DL) striatum mice that had been given MPTP showed a 63% and 83% loss of tyrosine hydroxylase and dopamine transporter expression, respectively, there were no changes in the nucleus accumbens or medial prefrontal cortex (mPFC). Furthermore, dopamine-1 receptor and vesicular glutamate transporter (VGLUT)-1 expression increased in the mPFC following DA loss. There were significant MPTP-induced decreases and increases in VGLUT-1 and VGLUT-2 expression, respectively, within the DL striatum. We propose that the behavioral decline following MPTP treatment may be associated with a change not only in cortical-cortical (VGLUT-1) glutamate function but also in striatal DA and glutamate (VGLUT-1/VGLUT-2) input.

Original languageEnglish (US)
Pages (from-to)1849-1864
Number of pages16
JournalJournal of Neuroscience Research
Volume93
Issue number12
DOIs
StatePublished - Dec 2015

Keywords

  • Cognition
  • Cued response task
  • Nigrostriatal depletion
  • Parkinson's disease
  • RRID:AB_11125338
  • RRID:AB_11125348
  • RRID:AB_2094980
  • RRID:AB_2190287
  • RRID:AB_2190727
  • RRID:AB_2193878
  • RRID:AB_2254574
  • RRID:AB_2302051
  • RRID:AB_2313787
  • RRID:AB_2340875
  • RRID:AB_476743
  • RRID:AB_887876
  • RRID:nif-0000-00313

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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