Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia.
Anatomical and molecular abnormalities of excitatory neurons in the dorsolateral prefrontal cortex (DLPFC) are found in schizophrenia. We hypothesized that brain-derived neurotrophic factor (BDNF), a protein capable of increasing pyramidal neuron spine density and augmenting synaptic efficacy of glutamate, may be abnormally expressed in the DLPFC of patients with schizophrenia. Using an RNase protection assay and Western blotting, we detected a significant reduction in BDNF mRNA (mean=23%) and protein (mean=40%) in the DLPFC of patients with schizophrenia compared to normal individuals. At the cellular level, BDNF mRNA was expressed at varying intensities in pyramidal neurons throughout layers II, III, V, and VI of DLPFC. In patients with schizophrenia; neuronal BDNF expression was decreased in layers III, V and VI. Our study demonstrates a reduction in BDNF production and availability in the DLPFC of schizophrenics, and suggests that intrinsic cortical neurons, afferent neurons, and target neurons may receive less trophic support in this disorder.
Weickert
C S
CS
Clinical Brain Disorders Branch, NIMH, IRP, NIH, Bethesda, MD 20892-1385, USA. shannowc@intra.nimh.nih.gov
Hyde
T M
TM
Lipska
B K
BK
Herman
M M
MM
Weinberger
D R
DR
Kleinman
J E
JE
D000293:Adolescent; D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D012559:Schizophrenia / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D018698:Glutamic Acid