Dopamine transporter mRNA levels are high in midbrain neurons vulnerable to MPTP.
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.
Sanghera
M K
MK
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75235-9070, USA.
Manaye
K
K
McMahon
A
A
Sonsalla
P K
PK
German
D C
DC
D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002352:Carrier Proteins / Q000096:biosynthesis*; D050483:Dopamine Plasma Membrane Transport Proteins; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020267:MPTP Poisoning; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D026901:Membrane Transport Proteins; D008636:Mesencephalon / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; C493215:Slc6a3 protein, mouse