Elevated postmortem striatal t-DARPP expression in schizophrenia and associations with DRD2/ANKK1 polymorphism.
BACKGROUND
Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) and calcineurin (CaN) have been implicated in the pathogenesis of schizophrenia because they function as molecular integrators of dopamine and glutamate signaling. DARPP-32 and CaN are mainly expressed in the caudate nucleus and putamen; however, a few postmortem brain studies have focused on DARPP-32 expression in striatum from patients with schizophrenia.


METHODS
We used immunoblotting techniques and postmortem tissue samples from patients with schizophrenia and from normal control individuals to examine the expression of two major DARPP-32 isoforms, full-length (FL-DARPP) and truncated (t-DARPP), and of CaN in the striatum. We also assessed whether there was any significant correlation between the expression levels of either protein and the A1 allele of Taq1A genotype in the dopamine D2 receptor (DRD2) gene/ankyrin-repeat containing kinase 1 (ANKK1) gene.


RESULTS
We found that the mean t-DARPP expression level in the caudate was higher in patients with schizophrenia than in control individuals (P<0.05) and the A1 allele of Taq1A genotype in DRD2/ANKK1 was significantly associated with elevated expression of t-DARPP in the caudate. Also, the A1 allele was significantly correlated with the total score of antemortem psychiatric symptoms.


CONCLUSIONS
These results may reflect potential molecular mechanisms important to the pathogenesis of schizophrenia.
Department of Neuropsychiatry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan. Electronic address: kunii@fmu.ac.jp.
Yasuto
Y
Kunii
Department of Neuropsychiatry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan.
Itaru
I
Miura
Department of Neuropsychiatry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan.
Junya
J
Matsumoto
Department of Neuropsychiatry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan.
Mizuki
M
Hino
Department of Neuropsychiatry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan.
Akira
A
Wada
Department of Neuropsychiatry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan.
Shin-ichi
S
Niwa
Department of Molecular Neurobiology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Niigata, Niigata 951-8585, Japan.
Hiroyuki
H
Nawa
Department of Molecular Neurobiology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Niigata, Niigata 951-8585, Japan.
Miwako
M
Sakai
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata, Niigata 951-8585, Japan.
Toshiyuki
T
Someya
Department of Pathology, Brain Research Institute, University of Niigata, 1-757 Asahimachi-dori, Niigata, Niigata 951-8585, Japan.
Hitoshi
H
Takahashi
Department of Pathology, Brain Research Institute, University of Niigata, 1-757 Asahimachi-dori, Niigata, Niigata 951-8585, Japan.
Akiyoshi
A
Kakita
Department of Neuropsychiatry, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan.
Hirooki
H
Yabe
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D019703:Calcineurin / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011180:Postmortem Changes; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D017448:Receptors, Dopamine D2; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases; D019703:Calcineurin
DARPP-32; Dopamine D2 receptor gene (DRD2); Schizophrenia; Taq1A polymorphism; Truncated DARPP