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

Neurobiol Dis. 2012 Feb;45(2):796-803. doi: 10.1016/j.nbd.2011.11.003. Epub 2011 Nov 13.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Animals
  • Auditory Cortex / metabolism
  • Auditory Cortex / pathology
  • Blotting, Western
  • Dendrites / metabolism
  • Dendrites / pathology*
  • Fluorescent Antibody Technique
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Microscopy, Confocal
  • Protein Serine-Threonine Kinases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Schizophrenia / metabolism*
  • Schizophrenia / pathology*

Substances

  • Guanine Nucleotide Exchange Factors
  • KALRN protein, human
  • Protein Serine-Threonine Kinases