Reductions in neurotrophin receptor mRNAs in the prefrontal cortex of patients with schizophrenia.
Patients with schizophrenia have reduced neurotrophin levels in their dorsolateral prefrontal cortex (DLPFC) compared to normal unaffected individuals. The tyrosine kinase-containing receptors, trkB and trkC, mediate the growth-promoting effects of neurotrophins and respond to changes in growth factor availability. We hypothesized that trkB and/or trkC expression would be altered in the DLPFC of patients with schizophrenia. We measured mRNA encoding the tyrosine kinase domain (TK+)-containing form of trkB and measured pan trkC mRNA in schizophrenics (N=14) and controls (N=15) using in situ hybridization. TrkB and trkC mRNAs were detected in large and small neurons in multiple cortical layers of the human DLPFC. We found significantly diminished expression of trkB(TK+) mRNA in large neurons in multiple cortical layers of patients as compared to controls, while small neurons also showed reductions in trkB(TK+) mRNA that did not reach statistical significance. In normals, strong positive correlations were found between trkB(TK+) mRNA levels and brain-derived neurotrophic factor (BDNF) mRNA levels among various neurons, while no correlation between BDNF and trkB(TK+) was found in patients with schizophrenia. TrkC mRNA was also reduced in the DLPFC of schizophrenics in large neurons in layers II, III, V and VI and in small neurons in layer IV. Since neurons in the DLPFC integrate and communicate signals to various cortical and subcortical regions, these reductions in growth factor receptors may compromise the function and plasticity of the DLPFC in schizophrenia.
Weickert
C S
CS
Clinical Brain Disorders Branch, National Institute of Mental Health, Division of Intramural Research Programs, National Institutes of Health, Bethesda, MD, USA. shannowc@intra.nih.gov
Ligons
D L
DL
Romanczyk
T
T
Ungaro
G
G
Hyde
T M
TM
Herman
M M
MM
Weinberger
D R
DR
Kleinman
J E
JE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D012016:Reference Values; D012559:Schizophrenia / Q000378:metabolism*; D018709:Statistics, Nonparametric
D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D020813:Receptor, trkB; D020812:Receptor, trkC