Dopaminergic abnormalities in select thalamic nuclei in schizophrenia: involvement of the intracellular signal integrating proteins calcyon and spinophilin.
OBJECTIVE
While both thalamic abnormalities and dopaminergic dysregulation have been separately implicated in the pathophysiology of schizophrenia, little is known about the possible dysfunction of molecules associated with dopaminergic neurotransmission in the thalamus in this illness. In this study, the authors studied this question by measuring in postmortem brain the expression of molecules associated with dopaminergic neurotransmission.


METHODS
Using in situ hybridization and receptor autoradiography, the authors determined in schizophrenia and comparison subjects 1) thalamic expression of the transcripts encoding the five dopamine receptors; 2) binding to the dopamine D(1), D(2), and D(3) receptors; 3) monoaminergic innervation as assessed by binding to the vesicular monoamine transporter; and 4) transcripts encoding three dopamine receptor-associated intracellular proteins (calcyon, spinophilin, and DARPP-32) that mediate integration of dopaminergic signaling with other neurotransmitter systems.


RESULTS
Both calcyon and spinophilin transcripts were significantly elevated in schizophrenia subjects. Monoaminergic innervation, as well as dopamine receptor transcripts and binding sites, were unaffected in this illness.


CONCLUSIONS
These data indicate that there are dopaminergic abnormalities in the thalamus in schizophrenia but that they are at the level of intracellular integration of dopamine signaling with other neurotransmitter systems, likely including glutamate, in thalamic neurons.
Clinton
Sarah M
SM
Mental Health Research Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI 48109-0720, USA. clintons@umich.edu
Ibrahim
Hisham M
HM
Frey
Kirk A
KA
Davis
Kenneth L
KL
Haroutunian
Vahram
V
Meador-Woodruff
James H
JH
D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism / Q000502:physiology; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology; D013787:Thalamic Nuclei / Q000378:metabolism* / Q000503:physiopathology; D014018:Tissue Distribution; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism; D000099273:Neurabins
D004298:Dopamine; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D050493:Vesicular Monoamine Transport Proteins; D000099273:Neurabins; C497928:PPP1R1B protein, human; C493452:SLC18A2 protein, human; C405464:calcyon