Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson's disease model

Anna Liisa Brownell, Kelly Canales, Y. Iris Chen, Bruce G. Jenkins, Christopher Owen, Elijahu Livni, Meixiang Yu, Francesca Cicchetti, Rosario Sanchez-Pernaute, Ole Isacson

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Neurophysiological studies of the brain in normal and Parkinson's disease (PD) patients have indicated intricate connections for basal ganglia-induced control of signaling into the motor cortex. To investigate if similar mechanisms are controlling function in the primate brain (Macaca fascicularis) after MPTP-induced neurotoxicity, we conducted PET studies of cerebral blood flow, oxygen and glucose metabolism, dopamine transporter, and D2 receptor function. Our observations after MPTP-induced dopamine terminal degeneration of the caudate and putamen revealed increased blood flow (15%) in the globus pallidus (GP), while blood flow was moderately decreased (15-25%) in the caudate, putamen, and thalamus and 40 % in the primary motor cortex (PMC). Oxygen extraction fraction was moderately increased (10-20%) in other brain areas but the thalamus, where no change was observable. Oxygen metabolism was increased in the GP and SMA (supplementary motor area including premotor cortex, Fig. 3) by a range of 20-40% and decreased in the putamen and caudate and in the PMC. Glucose metabolism was decreased in the caudate, putamen, thalamus, and PMC (range 35-50%) and enhanced in the GP by 15%. No change was observed in the SMA. In the parkinsonian primate, [11C]CFT (2β -carbomethoxy-3β-(4-fluorophenyltropane) dopamine transporter binding was significantly decreased in the putamen and caudate (range 60-65%). [ 11C]Raclopride binding of dopamine D2 receptors did not show any significant changes. These experimental results obtained in primate studies of striato-thalamo-cortico circuitry show a similar trend as hypothetized in Parkinson's disease-type degeneration.

Original languageEnglish (US)
Pages (from-to)1064-1075
Number of pages12
JournalNeuroImage
Volume20
Issue number2
DOIs
StatePublished - Oct 1 2003

Keywords

  • MPTP
  • Parkinson's disease
  • Positron emission tomography
  • Volume rendering

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

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