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Altered prefrontal cortical MARCKS and PPP1R9A mRNA expression in schizophrenia and bipolar disorder

Glenn T Konopaske1, Sivan Subburaju1, Joseph T Coyle1

  • 1Mailman Research Center, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.

Schizophrenia Research
|March 12, 2015
PubMed
Abstract

Insights

Gene expression changes in the dorsolateral prefrontal cortex (DLPFC) may contribute to spine loss in schizophrenia and bipolar disorder. MARCKS and PPP1R9A gene mRNA levels were altered, potentially impacting NMDA receptor signaling and neuronal structure.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Psychiatry

Background:

  • Dendritic spine loss observed in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia and bipolar disorder subjects.
  • Previous research indicated potential links between actin cytoskeleton regulation and spine morphology.

Purpose of the Study:

  • To investigate the correlation between mRNA expression of candidate genes regulating the actin cytoskeleton and dendritic spine loss.
  • To identify specific genes and pathways involved in synaptic alterations in psychiatric disorders.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) used to assess mRNA expression of five candidate genes (IGF1R, MARCKS, PPP1R9A, PTPRF, ARHGEF2) in DLPFC.
  • Microarray data analysis to identify candidate genes.
  • Functional pathway analysis to explore gene interactions with actin cytoskeleton-regulatory pathways.

Main Results:

  • MARCKS mRNA expression was elevated in both schizophrenia and bipolar disorder subjects.
  • PPP1R9A mRNA expression was increased in bipolar disorder subjects.
  • IGF1R mRNA expression showed a negative correlation with dendrite length, though no significant group differences were found. MARCKS and PPP1R9A did not directly correlate with spine loss but interact with NMDA receptor signaling pathways.

Conclusions:

  • MARCKS and PPP1R9A gene expression alterations may contribute to spine loss in schizophrenia and bipolar disorder.
  • These genes likely influence spine structure and function through interactions with NMDA receptor signaling pathways, potentially indirectly.
Keywords:
Actin cytoskeletonBipolar disorderDorsolateral prefrontal cortexPostmortemSchizophreniaqRT-PCR

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