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: 4.01). 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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Available from: Robert R Conley, Aug 31, 2015
    • "It also plays a crucial role in the pathophysiology of various neurodegenerative (Durany et al. 2000) and psychiatric disorders including depression (Autry and Monteggia 2012). In the brain of depressive patients, BDNF level is lower and correlates with reduced hippocampus and prefrontal cortex size (Pandey et al. 2008;Thompson Ray et al. 2011). BDNF is decreased not only in the brain but also in the serum of patients with bipolar disorders and depression (Cunha et al. 2006;Palomino et al. 2006). "
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    ABSTRACT: Rationale Depression is highly prevalent in diabetes (DM). Brain-derived neurotrophic factor (BDNF) which is mainly regulated by the endoplasmic reticulum chaperon sigma-1 receptor (S1R) plays a relevant role in the development of depression. Objectives We studied the dose-dependent efficacy of S1R agonist fluvoxamine (FLU) in the prevention of DM-induced depression and investigated the significance of the S1R-BDNF pathway. Methods We used streptozotocin to induce DM in adult male rats that were treated for 2 weeks p.o. with either different doses of FLU (2 or 20 mg/bwkg) or FLU + S1R antagonist NE100 (1 mg/bwkg) or vehicle. Healthy controls were also enrolled. Metabolic, behaviour, and neuroendocrine changes were determined, and S1R and BDNF levels were measured in the different brain regions. Results In DM rats, immobility time was increased, adrenal glands were enlarged, and thymuses were involuted. FLU in 20 mg/bwkg, but not in 2 mg/bwkg dosage, ameliorated depression-like behaviour. S1R and BDNF protein levels were decreased in DM, while FLU induced SIR-BDNF production. NE100 suspended all effects of FLU. Conclusions We suggest that disturbed S1R-BDNF signaling in the brain plays a relevant role in DM-induced depression. The activation of this cascade serves as an additional target in the prevention of DM-associated depression.
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    • "Retinoid signaling, brain-derived neurotropic factor (BDNF) and the gene that encodes its high-affinity receptor, tropomycin kinase B (TrkB), have received considerable attention in human studies of suicidal behavior. Some of these studies have revealed that people who commit suicide have decreased mRNA and/or protein levels of BDNF, TrkB, or both, in the PFC (Ernst et al., 2009; Maussion et al., 2014; Pandey et al., 2008). Their decreased expression correlated with hypermethylation of the BDNF promoters in exons 4 and 9 (Roth et al., 2009). "
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    Full-text · Article · Sep 2015 · Journal of Psychiatric Research
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    • "Immunolabeling and mRNA levels of TrkA and TrkC were decreased in the hippocampus of suicide subjects with major depression when compared to normal subjects and p75NTR was increased [32]. In post-mortem brain of teenage suicide victims TrkB mRNA levels were decreased in both prefrontal cortex and hippocampus [33]. "
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