Disease-specific alterations in glutamatergic neurotransmission on inhibitory interneurons in the prefrontal cortex in schizophrenia

• Published in: Brain research Vol. 1218; pp. 267 - 277
• Main Authors: Woo, Tsung-Ung W., Kim, Amy M., Viscidi, Emma
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 07.07.2008
• Subjects: Adult; Aged; Aged, 80 and over; Bipolar disorder; Bipolar Disorder - pathology; Cohort Studies; Female; GABA; Glutamate Decarboxylase - genetics; Glutamate Decarboxylase - metabolism; Humans; Interneurons - physiology; Male; Middle Aged; Neurology; NMDA; Postmortem Changes; Postmortem studies; Prefrontal Cortex - pathology; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; Schizophrenia; Schizophrenia - pathology; GABA; NMDA; Schizophrenia; Bipolar disorder; Postmortem studies
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.03.092

Glutamatergic modulation of inhibitory interneurons plays a crucial role in shaping the flow of information in the cerebral cortex. In a cohort of postmortem human brains from schizophrenia ( n = 20), bipolar disorder ( n = 20) and normal control ( n = 20) subjects, we colocalized the mRNA for the N-methyl- d-aspartate (NMDA) receptor NR2A subunit, labeled with [ 35S], and the mRNA for the γ-aminobutyric acid (GABA) synthesizing enzyme glutamic acid decarboxylase (GAD) 67, labeled with digoxigenin. We found that the density of GAD 67+ neurons in layers 2–5 of the prefrontal cortex was decreased by 27–36% in both schizophrenia and bipolar disorder. In addition, the density of the GAD 67+/NR2A+ neurons was decreased by 57% and 49% in layers 3 and 4, respectively, in schizophrenia, but it was unchanged in bipolar disorder. These findings raise the possibility that glutamatergic innervation of inhibitory interneurons via the NMDA receptor in the prefrontal cortex may be selectively altered in schizophrenia.