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

NEUROBIOLOGY OF DISEASE

卷:45

Article

Deo, Anthony J.^1,2  Cahill, Michael E.³  Li, Siyu⁴  Goldszer, Isaac¹  Henteleff, Ruth¹  VanLeeuwen, Jon-Eric³  Rafalovich, Igor³  Gao, Ruoqi³  Stachowski, Erin K.⁵  Sampson, Allan R.⁴  Lewis, David A.^1,5  Penzes, Peter^3,6  Sweet, Robert A.^1,7,8 

[1] Univ Pittsburgh, Sch Med, Dept Psychiat, Translat Neurosci Program, Pittsburgh, PA 15213 USA

[2] Univ Pittsburgh, Sch Med, Phys Scientist Training Program, Pittsburgh, PA 15213 USA

[3] Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA

[4] Univ Pittsburgh, Dept Stat, Pittsburgh, PA 15213 USA

[5] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15213 USA

[6] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA

[7] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA

[8] VA Pittsburgh Healthcare Syst, Educ & Clin Ctr, VISN Mental Illness Res 4, Pittsburgh, PA USA

关键词: Endophenotypes;    Kalirin;    Schizophrenia;    Schizoaffective;    Auditory cortex;    Dendrite;   

DOI  :  10.1016/j.nbd.2011.11.003

来源: Elsevier

【 摘 要 】

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. Published by Elsevier Inc.

【 授权许可】

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