Increased expression of Kalirin-9 in the auditory cortex of schizophrenia subjects: Its role in dendritic pathology

• Published in: Neurobiology of disease Vol. 45; no. 2; pp. 796 - 803
• Main Authors: Deo, Anthony J., Cahill, Michael E., Li, Siyu, Goldszer, Isaac, Henteleff, Ruth, VanLeeuwen, Jon-Eric, Rafalovich, Igor, Gao, Ruoqi, Stachowski, Erin K., Sampson, Allan R., Lewis, David A., Penzes, Peter, Sweet, Robert A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2012; Elsevier
• Subjects: Adult; Animals; Auditory cortex; Auditory Cortex - metabolism; Auditory Cortex - pathology; Blotting, Western; Dendrite; Dendrites - metabolism; Dendrites - pathology; Endophenotypes; Fluorescent Antibody Technique; Guanine Nucleotide Exchange Factors - metabolism; Humans; Kalirin; Microscopy, Confocal; Neurology; Protein Serine-Threonine Kinases - metabolism; Rats; Rats, Sprague-Dawley; Schizoaffective; Schizophrenia; Schizophrenia - metabolism; Schizophrenia - pathology; Kalirin; Schizophrenia; Schizoaffective; Endophenotypes; Auditory cortex; Dendrite
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2011.11.003

Reductions in dendritic arbor length and complexity are among the most consistently replicated changes in neuronal structure in post mortem studies of cerebral cortical samples from subjects with schizophrenia, however, the underlying molecular mechanisms have not been identified. This study is the first to identify an alteration in a regulatory protein which is known to promote both dendritic length and arborization in developing neurons, Kalirin-9. We found Kalirin-9 expression to be paradoxically increased in schizophrenia. We followed up this observation by overexpressing Kalirin-9 in mature primary neuronal cultures, causing reduced dendritic length and complexity. Kalirin-9 overexpression represents a potential mechanism for dendritic changes seen in schizophrenia. ► Reduced dendritic length and complexity has been consistently found in studies of the cerebral cortex in schizophrenia. ► Protein expression of the Kalirin isoform, Kalirin-9, was increased in cortical gray matter from schizophrenia subjects. ► Over-expression of Kalirin-9 in mature cortical neuron cultures resulted in reduced dendritic length and complexity. ► Increased Kalirin-9 expression is a potential mechanism contributing to dendritic pathology in schizophrenia.