Promoter specific alterations of brain-derived neurotrophic factor mRNA in schizophrenia

J. Wong, Thomas Hyde, H. L. Cassano, A. Deep-Soboslay, Joel Kleinman, C. Shannon Weickert

Research output: Contribution to journalArticle

Abstract

The brain-derived neurotrophic factor (BDNF) gene contains multiple 5' promoters which generate alternate transcripts. Previously, we found that pan-BDNF mRNA and protein are reduced in the dorsolateral prefrontal cortex (DLPFC) from patients with schizophrenia. In this study, we determined which of the four most abundant and best characterized BDNF alternate transcripts, I-IX, II-IX, IV-IX, and VI-IX are altered in schizophrenia. Using a cohort from the NIMH, USA, we found that BDNF II-IX mRNA was significantly reduced in the DLPFC of patients with schizophrenia, and we replicated this finding using a second cohort from Sydney, Australia. Moreover, we show that BDNF protein expression [including prepro (~32 kDa), pro (~28 kDa) and mature (~14 kDa) BDNF] is reduced in the DLPFC of patients with schizophrenia. We next determined the regional specificity of the BDNF mRNA reduction by measuring BDNF transcripts in the parietal cortex and hippocampus and found no significant changes. The effect of antipsychotics on BDNF alternate transcript expression was also examined and we found no relationship between BDNF mRNA expression and antipsychotic use. As schizophrenic patients are often prescribed antidepressants which can up-regulate expression of BDNF, we investigated the relationship between antidepressant treatment and BDNF transcript expression. All four BDNF transcripts were significantly up-regulated in schizophrenic patients treated with antidepressants. Moreover, we found significant reductions in BDNF transcripts II-IX and IV-IX in the parietal cortex and VI-IX in the hippocampus of patients with schizophrenia who did not have a history of treatment with antidepressants. This suggests that down-regulation of at least one out of four major BDNF transcripts occurs in various brain regions of patients with schizophrenia, particularly in the DLPFC which appears to have the most robust BDNF deficit in schizophrenia.

Original languageEnglish (US)
Pages (from-to)1071-1084
Number of pages14
JournalNeuroscience
Volume169
Issue number3
DOIs
StatePublished - Sep 2010
Externally publishedYes

Fingerprint

Brain-Derived Neurotrophic Factor
Schizophrenia
Messenger RNA
Prefrontal Cortex
Antidepressive Agents
Parietal Lobe
Nerve Growth Factors
Antipsychotic Agents
Hippocampus
National Institute of Mental Health (U.S.)
Factor IX
Prothrombin

Keywords

  • Antidepressant
  • Brain-derived neurotrophic factor
  • DLPFC
  • Interneurons
  • Postmortem
  • Schizophrenic

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Promoter specific alterations of brain-derived neurotrophic factor mRNA in schizophrenia. / Wong, J.; Hyde, Thomas; Cassano, H. L.; Deep-Soboslay, A.; Kleinman, Joel; Weickert, C. Shannon.

In: Neuroscience, Vol. 169, No. 3, 09.2010, p. 1071-1084.

Research output: Contribution to journalArticle

Wong, J. ; Hyde, Thomas ; Cassano, H. L. ; Deep-Soboslay, A. ; Kleinman, Joel ; Weickert, C. Shannon. / Promoter specific alterations of brain-derived neurotrophic factor mRNA in schizophrenia. In: Neuroscience. 2010 ; Vol. 169, No. 3. pp. 1071-1084.
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