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Brain-derived Neurotrophic Factor (Brain-derive + neurotrophic_factor)
Selected AbstractsEffects of 4-week Treatment with Lithium and Olanzapine on Levels of Brain-derived Neurotrophic Factor, B-Cell CLL/Lymphoma 2 and Phosphorylated Cyclic Adenosine Monophosphate Response Element-binding Protein in the Sub-regions of the HippocampusBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009Michael D. Hammonds It has been suggested that up-regulation of neurotrophic and neuroprotective factors including brain-derived neurotrophic factor (BDNF) and B-cell CLL/lymphoma 2 (Bcl-2) may underlie these neuroplastic actions of the drug. Olanzapine, an atypical anti-psychotic drug, has been shown to be an effective mood stabilizer. Olanzapine also has neurotrophic and neuroprotective actions, and these actions may underlie the efficacy of the drug for bipolar disorder and schizophrenia. However, the molecular mechanism by which the drug produces the neuroplastic actions is poorly understood. To understand a common molecular mechanism underlying the neuroplastic actions of lithium and olanzapine, we assessed the effect of 4-week lithium and olanzapine treatment on the levels of BDNF, Bcl-2 and cyclic adenosine monophosphate response element-binding protein (CREB), a transcription factor involved in expression of BDNF and Bcl-2, in the dentate gyrus and hippocampal area CA1. Our results show that 4-week treatment with both olanzapine and lithium increases the levels of Bcl-2 and CREB in the dentate gyrus and hippocampal area CA1. Four-week lithium treatment up-regulates BDNF in the dentate gyrus, and 4-week olanzapine treatment marginally did so. Neither drug altered BDNF levels in area CA1. These results suggest that the up-regulation of Bcl-2 and CREB may underlie the neuroplastic actions of olanzapine and lithium. [source] BIT/SHPS-1 Enhances Brain-Derived Neurotrophic Factor-Promoted Neuronal Survival in Cultured Cerebral Cortical NeuronsJOURNAL OF NEUROCHEMISTRY, Issue 4 2000Toshiyuki Araki Abstract: Brain-derived neurotrophic factor (BDNF) activates a variety of signaling molecules to exert various functions in the nervous system, including neuronal differentiation, survival, and regulation of synaptic plasticity. Previously, we have suggested that BIT/SHPS-1 (brain immunoglobulin-like molecule with tyrosine-based activation motifs/SHP substrate 1) is a substrate of Shp-2 and is involved in BDNF signaling in cultured cerebral cortical neurons. To elucidate the biological function of BIT/SHPS-1 in cultured cerebral cortical neurons in connection with its role in BDNF signaling, we generated recombinant adenovirus vectors expressing the wild type of rat BIT/SHPS-1 and its 4F mutant in which all tyrosine residues in the cytoplasmic domain of BIT/SHPS-1 were replaced with phenylalanine. Overexpression of wild-type BIT/SHPS-1, but not the 4F mutant, in cultured cerebral cortical neurons induced tyrosine phosphorylation of BIT/SHPS-1 itself and an association of Shp-2 with BIT/SHPS-1 even without addition of BDNF. We found that BDNF-promoted survival of cultured cerebral cortical neurons was enhanced by expression of the wild type and also 4F mutant, indicating that this enhancement by BIT/SHPS-1 does not depend on its tyrosine phosphorylation. BDNF-induced activation of mitogen-activated protein kinase was not altered by the expression of these proteins. In contrast, BDNF-induced activation of Akt was enhanced in neurons expressing wild-type or 4F mutant BIT/SHPS-1. In addition, LY294002, a specific inhibitor of phosphatidylinositol 3-kinase, blocked the enhancement of BDNF-promoted neuronal survival in both neurons expressing wild-type and 4F mutant BIT/SHPS-1. These results indicate that BIT/SHPS-1 contributes to BDNF-promoted survival of cultured cerebral cortical neurons, and that its effect depends on the phosphatidylinositol 3-kinase-Akt pathway. Our results suggest that a novel action of BIT/SHPS-1 does not occur through tyrosine phosphorylation of BIT/SHPS-1 in cultured cerebral cortical neurons. [source] Circulating levels of brain-derived neurotrophic factor correlate with disease severity in the intrinsic type of atopic dermatitisALLERGY, Issue 12 2006U. Raap Background:, Recent studies have shed light on the complex regulation of genetic, environmental, immunologic and pharmacologic factors, which contribute to the development of atopic dermatitis (AD). However, it is still unclear to which extent neuroimmune mediators have a role in AD. Aims of the study:, To assess peripheral neurotrophin levels and their correlation with scoring atopic dermatitis (SCORAD) scores in both the intrinsic and extrinsic types of AD compared with patients with psoriasis and nonatopic healthy subjects. Methods:, Levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were assessed in peripheral blood with enzyme-linked immunosorbent assay. Based on IgE-mediated sensitization, AD was divided into the extrinsic and intrinsic type. Severity of AD was assessed with SCORAD score and with psoriasis area and severity index (PASI) in patients with psoriasis. Results:, Brain-derived neurotrophic factor and NGF were detectable in all the subjects studied. However, the levels of both neurotrophins were significantly higher in patients with extrinsic and intrinsic types of AD compared with patients with psoriasis and nonatopic healthy subjects (NGF: P < 0.001, BDNF: P < 0.001). NGF and BDNF levels were similar in the intrinsic and extrinsic type of AD. There was a significant correlation between BDNF and SCORAD score only in patients with the intrinsic type of AD (r = 0.57, P < 0.05). Conclusions:, This study shows for the first time that NGF and BDNF are increased in both, the extrinsic type and the intrinsic type of AD. This finding points to a similar pathophysiologic background implicating a neuroimmune network in both variants of this chronic inflammatory skin disease. Future studies are needed to show the direct mechanisms of neurotrophin action in chronic inflammatory skin. [source] Differential changes in brain-derived neurotrophic factor and extracellular signal-regulated kinase in rat primary afferent pathways with colitisNEUROGASTROENTEROLOGY & MOTILITY, Issue 8 2008L.-y. Qiao Abstract, Brain-derived neurotrophic factor (BDNF) has been postulated to participate in inflammation-induced visceral hypersensitivity by modulating the sensitivity of visceral afferents through the activation of intracellular signalling pathways such as the extracellular signal-regulated kinase (ERK) pathway. In the current study, we assessed the expression levels of BDNF and phospho-ERK in lumbosacral dorsal root ganglia (DRG) and spinal cord before and during tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in rats with real-time PCR, ELISA, western blot and immunohistochemical techniques. BDNF mRNA and protein levels were increased in L1 and S1 but not L6 DRG when compared with control (L1: two- to five-fold increases, P < 0.05; S1: two- to three-fold increases, P < 0.05); however, BDNF protein but not mRNA level was increased in L1 and S1 spinal cord when compared with control. In parallel, TNBS colitis significantly induced phospho-ERK1/2 expression in L1 (four- to five-fold, P < 0.05) and S1 (two- to three-fold, P < 0.05) but not in L6 spinal cord levels. Immunohistochemistry results showed that the increase in phospho-ERK1/2 expression occurred at the region of the superficial dorsal horn and grey commisure of the spinal cord. In contrast, there was no change in phospho-ERK5 in any level of the spinal cord examined during colitis. The regional and time-specific changes in the levels of BDNF mRNA, protein and phospho-ERK with colitis may be a result of increased transcription of BDNF in DRG and anterograde transport of BDNF from DRG to spinal cord where it activates intracellular signalling molecules such as ERK1/2. [source] Plasminogen activator inhibitor 1 gene polymorphisms and mirtazapine responses in Koreans with major depressionASIA-PACIFIC PSYCHIATRY, Issue 3 2009Hun Soo Chang PhD Abstract Introduction: Brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of mental disorders and in the mechanism of action of antidepressant medications. The mature form of BDNF is derived from proBDNF through tissue type plasminogen activator (tPA) and the plasminogen system in the brain, which is regulated by an endogenous inhibitor, plasminogen activator inhibitor (PAI). Therefore, PAI may be involved in the development of major depressive disorder (MDD) and its response to antidepressant treatment. The present study determined the relationship between the 4G/5G polymorphism in the PAI1 gene and the clinical outcome of mirtazapine treatment in 271 Korean MDD patients. Methods: We tested the association between the polymorphism and response to mirtazapine treatment or percentage decrease of the 21-item Hamilton Depression Rating (HAMD21) scores using multiple logistic and linear regression analysis. Results: PAI1 4G/5G genotypes and allele distributions were comparable between responders and non-responders during the treatment period. Similarly, linear regression showed no association between genotypes or alleles and the percentage decline in total HAMD21 with mirtazapine treatment. In the analysis of symptomatic subscores, the percentage decline in the psychic anxiety and delusion scores after 4 weeks of mirtazapine treatment showed a statistical trend to a difference among genotypes, although it was not statistically significance. Discussion: In this first pharmacogenetics study of the PAI1 4G/5G polymorphism and mirtazapine treatment response, our results do not support the hypothesis that this polymorphism is involved in the therapeutic response to mirtazapine. [source] | ||||||||||