N-methyl-D-aspartate receptor expression in parvalbumin-containing inhibitory neurons in the prefrontal cortex in bipolar disorder.
OBJECTIVE
Inhibitory neural circuits and the glutamatergic regulation of these circuits in the cerebral cortex appear to be disturbed in bipolar disorder. In this study, we addressed the hypothesis that, in the prefrontal cortex (PFC), disturbances of glutamatergic regulation of the class of inhibitory neurons that contain the calcium buffer parvalbumin (PV) via N-methyl-D-aspartate (NMDA) receptor may contribute to the pathophysiology of bipolar disorder.


METHODS
We used double in situ hybridization with a sulfur-35-labeled riboprobe for the NR2A subunit of the NMDA receptor and a digoxigenin-labeled riboprobe for PV in a cohort of 18 subjects with bipolar disorder and 18 demographically matched normal control subjects.


RESULTS
We observed no differences in the relative density and laminar distribution of the PV-expressing neurons between subjects with bipolar disorder and matched normal control subjects. Furthermore, the density of the PV neurons that co-expressed NR2A messenger RNA (mRNA) or the cellular expression of NR2A mRNA in the PV neurons that exhibited a detectable level of this transcript was unaltered in subjects with bipolar disorder.


CONCLUSIONS
These findings suggest that, in the PFC, glutamatergic regulation of PV-containing inhibitory neurons via NR2A-containing NMDA receptors does not appear to be altered in bipolar disorder. However, the possibility that other subsets of gamma-aminobutyric acid (GABA) neurons or other glutamate receptor subtypes are affected cannot be excluded.
Program for Cellular Neuropathology, McLean Hospital, Belmont, MA 02478, USA.
Byron Ky
BK
Bitanihirwe
Maribel P
MP
Lim
Tsung-Ung W
TU
Woo
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000473:pathology*; D002452:Cell Count; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009433:Neural Inhibition; D009474:Neurons / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
C120997:NR2A NMDA receptor; D010320:Parvalbumins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate