Cocaine abuse elevates alpha-synuclein and dopamine transporter levels in the human striatum.
Direct protein interactions between the dopamine transporter and alpha-synuclein demonstrate that dopamine uptake function is modulated by alpha-synuclein. We report here that chronic cocaine abuse results in an increase in alpha-synuclein expression in the human striatum. Immunoblot analysis in the ventral putamen showed that alpha-synuclein protein was increased in striatal synaptosomes from cocaine users compared with age-matched drug-free controls. [H]-Dopamine transporter uptake was increased in parallel with 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane binding to the dopamine transporter. The increase in alpha-synuclein protein was more marked in the ventromedial sectors of the striatum than in the dorsal caudate nucleus. These results demonstrate concomitant regulation of alpha-synuclein and dopamine transporter binding and function in human striatal synaptic terminals isolated from cocaine abusers. Overexpression of alpha-synuclein may play a role in cocaine-induced plasticity and regulation of dopamine synaptic tone.
Qin
Yujing
Y
Department of Neurology, University of Miami School of Medicine, Miami, FL 33101, USA.
Ouyang
Qinjie
Q
Pablo
John
J
Mash
Deborah C
DC
D000222:Adaptation, Physiological / Q000187:drug effects; D002908:Chronic Disease; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D004298:Dopamine