Dopamine transporter mRNA content in human substantia nigra decreases precipitously with age.
The dopamine transporter is the primary means of inactivating synaptic dopamine as well as a major site of action for psychostimulants (such as cocaine and amphetamine) and for neurotoxins that induce parkinsonism. In the present study, a human dopamine transporter partial cDNA clone obtained by polymerase chain reaction exhibited 87% and 89% identity at the nucleic acid and amino acid levels, respectively, with transmembrane domains 3-5 of the rat homolog. This clone was used to quantitate human dopamine transporter mRNA by nuclease protection assay. The postmortem content of dopamine transporter mRNA in the substantia nigrae of 18- to 57-yr-old subjects was relatively constant, while in subjects greater than 57 yr old, a precipitous (greater than 95%) decline in substantia nigra dopamine transporter mRNA was evident. In contrast, tyrosine hydroxylase mRNA in the same samples declined in a linear manner with increasing age. In situ hybridization experiments confirmed the profound loss of dopamine transporter gene expression in melanin-positive (presumptive dopamine) nigral neurons. These data may begin to shed light on compensatory changes occurring in human dopamine neurons during normal aging.
Department of Psychiatry (Cellular and Clinical Neurobiology Program), Wayne State University School of Medicine, Detroit, MI.
M J
MJ
Bannon
M S
MS
Poosch
Y
Y
Xia
D J
DJ
Goebel
B
B
Cassin
G
G
Kapatos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D015870:Gene Expression; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000502:physiology; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013378:Substantia Nigra / Q000254:growth & development / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine