Article

Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims

Department of Psychiatry, University of Illinois at Chicago, College of Medicine, Chicago, IL, USA.
The International Journal of Neuropsychopharmacology (Impact Factor: 5.26). 08/2008; 11(8):1047-61. DOI: 10.1017/S1461145708009000
Source: PubMed

ABSTRACT Teenage suicide is a major public health concern, but its neurobiology is not very well understood. Stress and major mental disorders are major risk factors for suicidal behaviour, and it has been shown that brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) are not only regulated by stress but are also altered in these illnesses. We therefore examined if BDNF/TrkB signalling is altered in the post-mortem brain of teenage suicide victims. Protein and mRNA expression of BDNF and of TrkB receptors were determined in the prefrontal cortex (PFC), Brodmann's Area 9 (BA 9), and hippocampus obtained from 29 teenage suicide victims and 25 matched normal control subjects. Protein expression was determined using the Western blot technique; mRNA levels by a quantitative RT-PCR technique. The protein expression of BDNF was significantly decreased in the PFC of teenage suicide victims compared with normal control subjects, whereas no change was observed in the hippocampus. Protein expression of TrkB full-length receptors was significantly decreased in both PFC and hippocampus of teenage suicide victims without any significant changes in the truncated form of TrkB receptors. mRNA expression of both BDNF and TrkB was significantly decreased in the PFC and hippocampus of teenage suicide victims compared with normal control subjects. These studies indicate a down-regulation of both BDNF and its receptor TrkB in the PFC and hippocampus of teenage suicide victims, which suggests that stress and altered BDNF may represent a major vulnerability factor in teenage suicidal behaviour.

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    • "In addition, the MEK/ERK pathway contributes to the neuroprotection provided by BDNF against glutamate-induced neuronal cell death (Almeida et al. 2005), and a recent study demonstrated that BDNF/TrkB signaling increases the transcription of GAD1 through a MAPK-dependent manner in cortical GABAergic interneurons (Sanchez-Huertas and Rico 2011). Moreover, Previous human postmortem brain studies demonstrated that BDNF and TrkB levels are decreased in dlPFC (BA 9) of teenage suicide victims (Pandey et al. 2008) and subjects with MDD (Dwivedi et al. 2003). Although this study suggests some interesting avenues into the possible linkage between the reduced levels of SLC1A2 and GAD1 in dlPFC in MDD, we believe that it should be viewed at this stage as exploratory. "
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    • "This neurotrophin is found throughout the brain and is particularly abundant in the hippocampus and cerebral cortex, areas thought to be critical for the control of mood, emotion, and cognition (Ernfors et al., 1990). A morphological study has shown that BDNF protein and mRNA expression, as well as that of its receptor, tyrosine kinase B (TrkB), are significantly decreased in the prefrontal cortex (PFC) and hippocampus of suicide victims compared to control subjects (Pandey et al., 2008). Furthermore, BDNF is also decreased in the PFC and hippocampus in an animal model of mania induced by dextroamphetamine (Frey et al., 2006). "
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    • "Patients frequently demonstrate sub-threshold symptoms with persistent cognitive impairment and functional decline (Goldstein et al., 2009). A morphological study has shown that protein and mRNA expression of BDNF and its receptor, tyrosine kinase B (TrkB), are significantly decreased in the prefrontal cortex (PFC) and hippocampus of suicide victims compared to control subjects (Pandey et al., 2008). Further, BDNF is also decreased in the PFC and hippocampus in an animal model of mania established using D-amphetamine (Frey et al., 2006). "
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