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.

0 Followers
 · 
87 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Suicide and suicidal behaviors are complex, heterogeneous phenomena that are thought to result from the interactions among distal factors increasing predisposition and proximal factors acting as precipitants. Epigenetic factors are likely to act both distally and proximally. Aspirational Goal 1 aims to find clear targets for suicide and suicidal behavior intervention through greater understanding of the interplay among the biological, psychological, and social risk and protective factors associated with suicide. This paper discusses Aspirational Goal 1, focusing on the research pathway related to epigenetics, suicide, and suicidal behaviors. Current knowledge on epigenetic factors associated with suicide and suicidal behaviors is reviewed and avenues for future research are discussed. Epigenetic factors are a promising area of further investigation in the understanding of suicide and suicidal behaviors and may hold clues to identifying targets or avenues for intervention.
    American Journal of Preventive Medicine 09/2014; 47(3):S144–S151. DOI:10.1016/j.amepre.2014.06.011 · 4.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Posttraumatic Stress Disorder (PTSD) is a prevalent, chronic, and disabling anxiety disorder that may develop following exposure to a traumatic event. The majority of individuals with PTSD often have comorbid psychiatric conditions such as major depression, generalized anxiety disorder, and substance use disorders, and are at increased risk for suicide. Despite the public health significance of PTSD, relatively little is known about the etiology or pathophysiology of this disorder, and pharmacotherapy development to date has been largely opportunistic instead of mechanism-based. One promising target for modulation is Tropomyosin Receptor Kinase B (TrkB), the receptor for Brain-Derived Neurotrophic Factor (BDNF), a signaling pathway important for neuronal plasticity, survival, and growth. The following discusses how genetic and environmental alterations to this signaling pathway may contribute to anatomical and functional changes in the hippocampus, amygdala, anterior cingulate cortex, ventromedial prefrontal cortex, and the nucleus accumbens. Changes in these brain regions may in turn contribute to the predisposition to or maintenance of some of the clinical manifestations of PTSD, including intrusive memories, hyperarousal, increased fear, and emotional numbing.
    10/2013; 2013(S4). DOI:10.4172/2167-1044.S4-006
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epilepsy and psychiatric comorbidities are frequently associated, but their common biological substrate is unknown. We have previously reported altered structural elements and neurotrophins (NTs) expression in mesial temporal lobe epilepsy (MTLE) patients with psychiatric comorbidities. NTs receptors can regulate neurotransmission and promote neuroplasticity, being important candidates in the regulation and manifestation of psychopatological states and seizure-related events. MTLE hippocampi of subjects without psychiatric history, MTLE¿+¿major depression, MTLE¿+¿interictal psychosis derived from epilepsy surgery, and control necropsies were investigated for p75NTR, TrkB, TrkA, and TrkC immunohistochemistry. Increased expression of p75NTR, decreased TrkA, unaltered TrkC, and complex alterations involving TrkB expression were seen in MTLE groups. Increased TrkB expression in patients without complete seizure remission and in those with secondarily generalized seizures was seen. Decreased p75NTR expression associated with interictal psychosis, and increased TrkB in those with psychosis or major depression was also reported, although their p75NTR/TrkB ratios were lower than in MTLE without psychiatric comorbidities. Our results provide evidence of alterations in expression of NTs receptors in the epileptogenic hippocampus that are differentially modulated in presence of psychiatric comorbidities. As already explored in animal models, even in chronic human MTLE increased TrkB expression, among other NT receptors alterations, may play a major role in seizure type, frequency and surgery outcome.
    07/2014; 2(1):81. DOI:10.1186/PREACCEPT-5185032491303487