Molecular NeuroscienceDopamine transporter mRNA levels are high in midbrain neurons vulnerable to MPTPSanghera, Manjit K.1; Manaye, Kebreten1; McMahon, Anne1; Sonsalla, Patricia K.2; German, Dwight C.1,3Author Information 1Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75235-9070, USA 2Department of Neurology, Robert Wood Johnson School of Medicine, Piscataway, NJ 08854-4535, USA 3Corresponding Author: Dwight C. German ACKNOWLEDGEMENTS: Research support by NIH (NS 30406), American Parkinson's Disease Association, Zigenbein Trust, James Webb Fund of the Dallas Foundation, Carl J. and Hortense M. Thomsen Chair in Alzheimer's Disease Research, and donations in honor of Richard D. Eiseman. The authors wish to thank Ms Judy Burdette for secretarial assistance. Website publication 3 October 1997 Received 6 August, 1997; accepted 17 August 1997 NeuroReport: October 20th, 1997 - Volume 8 - Issue 15 - p 3327-3331 Buy Abstract THE neurotoxin MPTP kills only certain midbrain dopaminergic (DA) neurons to produce a model of Parkinson's disease. The dopamine transporter (DAT) is important to MPTP toxicity because to be neurotoxic, an MPTP metabolite must first gain access to the DA neuron via the DAT. Also, MPTP is less toxic to DA neurons that contain the putative neuroprotective calcium-binding protein calbindin-D28k (CB). The present study examined the relative importance of DAT activity and CB for cellular vulnerability to MPTP-induced degeneration in the C57BL/6 mouse. Cells that were vulnerable to MPTP were found to contain high levels of DAT mRNA, whereas cells that were not vulnerable contained low levels. Also, the few substantia nigra cells remaining after a toxic dose of MPTP contained only low levels of DAT mRNA. However, there was not a strong relationship between cellular resistance to MPTP toxicity and cells containing CB. These data provide in vivo evidence for a direct correlation between midbrain cellular vulnerability to MPTP toxicity and the activity of the DAT. © Lippincott-Raven Publishers.