Dopamine receptor signaling molecules are altered in elderly schizophrenic cortex.
Alterations of molecules that mediate dopaminergic signal transduction have been found in schizophrenia, supporting the hypothesis of altered dopaminergic neurotransmission in this illness. To further explore this hypothesis, the authors measured transcript expression of three proteins involved in dopamine (DA) signaling in postmortem dorsolateral prefrontal and anterior cingulate cortex of elderly schizophrenic subjects and a comparison group. The transcript encoding calcyon, a protein that potentiates crosstalk between D1 DA receptors and Gq/11-linked receptors, was increased in schizophrenic prefrontal and cingulate cortex by 25%. Transcript levels of spinophilin, a protein enriched in dendritic spines that modulates excitatory neurotransmission, were increased 22% in dorsolateral prefrontal cortex but were unchanged in anterior cingulate cortex in schizophrenia. Levels of DARPP-32 mRNA, a downstream effector of dopaminergic neurotransmission, were similar in both groups for both cortical groups. These alterations in spinophilin and calcyon mRNA levels in schizophrenic prefrontal and cingulate cortex provide further evidence of altered dopaminergic neurotransmission in this illness.
Baracskay
Karen L
KL
Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan, USA.
Haroutunian
Vahram
V
Meador-Woodruff
James H
JH
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology*; D003627:Data Interpretation, Statistical; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D017397:Prefrontal Cortex / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism / Q000502:physiology*; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D000099273:Neurabins
D014150:Antipsychotic Agents; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D000099273:Neurabins; C497928:PPP1R1B protein, human; C405464:calcyon