Transcriptional dysregulation of γ-aminobutyric acid transporter in parvalbumin-containing inhibitory neurons in the prefrontal cortex in schizophrenia

Psychiatry Res. 2014 Dec 30;220(3):1155-9. doi: 10.1016/j.psychres.2014.09.016. Epub 2014 Oct 2.

Abstract

Parvalbumin (PV)-containing neurons are functionally compromised in schizophrenia. Using double in situ hybridization in postmortem human prefrontal cortex, we found that the messenger RNA (mRNA) for the γ-aminobutyric acid (GABA) transporter GAT-1 was undetectable in 22-41% of PV neurons in layers 3-4 in schizophrenia. In the remaining PV neurons with detectable GAT-1 mRNA, transcript expression was decreased by 26% in layer 3. Hence, the dysfunction of PV neurons involves the molecular dysregulation of presynaptic GABA reuptake.

Keywords: Parvalbumin; Schizophrenia; γ-aminobutyric acid transporter-1.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • GABA Plasma Membrane Transport Proteins / genetics*
  • Gene Expression Regulation*
  • Humans
  • Male
  • Middle Aged
  • Neural Inhibition / genetics*
  • Neural Inhibition / physiology*
  • Neurons / metabolism
  • Parvalbumins / metabolism*
  • Prefrontal Cortex / pathology
  • Prefrontal Cortex / physiopathology*
  • RNA, Messenger / metabolism
  • Schizophrenia / genetics*
  • Schizophrenia / pathology
  • Schizophrenia / physiopathology
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • GABA Plasma Membrane Transport Proteins
  • Parvalbumins
  • RNA, Messenger
  • gamma-Aminobutyric Acid