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rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-8-10
pubmed:abstractText
The cerebral frontal cortex of patients who had schizophrenia shows elevated levels of RNA for calcium/calmodulin-dependent protein kinase II beta (CaMKIIbeta). In addition, recent research shows that animal models for schizophrenia, such as amphetamine-sensitized rats, consistently show elevated levels of D2 receptors in their high-affinity state (D2(High)), the major target for antipsychotic medication. The present study was done, therefore, to examine whether an alteration in the levels of CaMKIIbeta could lead to altered levels of D2(High) receptors. We found that the CaMKII inhibitor, KN-93, markedly reduced D2(High) states in rat striatum. In addition, we studied heterozygous CaMKIIalpha knock-out mice that show features analogous to schizophrenia. The striata of these mice revealed a 2.8-fold increase in D2(High) receptors. In frontal cortex of the heterozygous CaMKIIalpha knock-out mice, CaMKIIalpha mRNA levels were reduced by 50%, while CaMKIIbeta mRNA levels were unaltered. In striatum, CaMKIIbeta mRNA levels were increased by 29%, suggesting the presence of a new CaMKIIbeta regulatory pathway not previously described. The elevated levels of CaMKIIbeta mRNA in the striatum suggest that this enzyme may increase D2(High) in animals and possibly in schizophrenia itself.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1098-2396
pubmed:author
pubmed:copyrightInfo
(c) 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
794-800
pubmed:meshHeading
pubmed-meshheading:20336626-Animals, pubmed-meshheading:20336626-Benzylamines, pubmed-meshheading:20336626-Calcium-Calmodulin-Dependent Protein Kinase Type 2, pubmed-meshheading:20336626-Corpus Striatum, pubmed-meshheading:20336626-Disease Models, Animal, pubmed-meshheading:20336626-Domperidone, pubmed-meshheading:20336626-Enzyme Inhibitors, pubmed-meshheading:20336626-Gene Expression Regulation, pubmed-meshheading:20336626-Hyperkinesis, pubmed-meshheading:20336626-Male, pubmed-meshheading:20336626-Mice, pubmed-meshheading:20336626-Mice, Inbred BALB C, pubmed-meshheading:20336626-Mice, Knockout, pubmed-meshheading:20336626-RNA, Messenger, pubmed-meshheading:20336626-Rats, pubmed-meshheading:20336626-Receptors, Dopamine D2, pubmed-meshheading:20336626-Schizophrenia, pubmed-meshheading:20336626-Sulfonamides, pubmed-meshheading:20336626-Tritium
pubmed:year
2010
pubmed:articleTitle
Hyperactive mice show elevated D2(High) receptors, a model for schizophrenia: Calcium/calmodulin-dependent kinase II alpha knockouts.
pubmed:affiliation
Department of Pharmacology, Medical Science Building, Room 4345, University of Toronto, Toronto, Ontario, Canada M5S 1A8. gabriela.novak@utoronto.ca
pubmed:publicationType
Journal Article