TY - JOUR
T1 - Dopamine transporter mRNA levels are high in midbrain neurons vulnerable to MPTP
AU - Sanghera, Manjit K.
AU - Manaye, Kebreten
AU - McMahon, Anne
AU - Sonsalla, Patricia K.
AU - German, Dwight C.
PY - 1997
Y1 - 1997
N2 - 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-D(28k) (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.
AB - 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-D(28k) (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.
KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
KW - Calbindin-D(28k) (CB)
KW - Dopamine transporter (DAT)
KW - Immunocytochemistry
KW - In situ hybridization
KW - Mice
KW - Midbrain dopaminergic (DA) neurons
UR - http://www.scopus.com/inward/record.url?scp=0030782462&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030782462&partnerID=8YFLogxK
U2 - 10.1097/00001756-199710200-00027
DO - 10.1097/00001756-199710200-00027
M3 - Article
C2 - 9351666
AN - SCOPUS:0030782462
SN - 0959-4965
VL - 8
SP - 3327
EP - 3331
JO - NeuroReport
JF - NeuroReport
IS - 15
ER -