Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov 10: 209-219
Center for Neural Repair, Department of Neurosciences 0626, University of California, San Diego, La Jolla, California 92093, USA. Nature Reviews Drug Discovery
(Impact Factor: 41.91).
03/2011; 10(3):209-19. DOI: 10.1038/nrd3366
The growth factor brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase receptor type B (TRKB) are actively produced and trafficked in multiple regions in the adult brain, where they influence neuronal activity, function and survival throughout life. The diverse presence and activity of BDNF suggests a potential role for this molecule in the pathogenesis and treatment of both neurological and psychiatric disorders. This article reviews the current understanding and future directions in BDNF-related research in the central nervous system, with an emphasis on the possible therapeutic application of BDNF in modifying fundamental processes underlying neural disease.
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Available from: Xiang Yang Zhang
- "BDNF in the blood may reflect the level of BDNF in the brain. Together, these findings confirm that BDNF is involved in schizophrenia (Nagahara and Tuszynski, 2011). A further finding of our present study is the increased IL-2, IL-6, and IL-8 levels but decreased TNF-a levels in chronic schizophrenia patients. "
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ABSTRACT: Brain-derived neurotrophic factor (BDNF) interacts with cytokines. Although both BDNF and cytokines occur at abnormal levels in schizophrenia patients, their interactions have not yet been examined. We therefore compared serum BDNF, TNF-α, interleukin (IL)-2, IL-6, and IL-8 levels in 92 chronically medicated schizophrenia patients and 60 healthy controls. We correlated these serum levels within these subject groups with each other and with clinical symptoms assessed according to the Positive and Negative Syndrome Scale (PANSS). Compared to the control group, the schizophrenia patients had significantly lower BDNF and TNF-α levels, and higher IL-2, IL-6, and IL-8 levels. The patients also showed a significant positive correlation between BDNF and both IL-2 and IL-8 levels, and low BDNF and TNF-α levels together were associated with poor performance on the PANSS cognitive factor. Thus, an interaction between cytokines and neurotrophic factors may be implicated in the pathophysiology of chronic schizophrenia. In particular, the cytokine TNF-α may interact with BNDF causing cognitive impairment.
Brain Behavior and Immunity 09/2015; DOI:10.1016/j.bbi.2015.09.014 · 5.89 Impact Factor
Available from: M. Foster Olive
- "The DNA methylation status and expression levels of BDNF in the prefrontal cortex were rescued by chronic intracerebroventricular treatment with a DNMT inhibitor. BDNF has emerged as having somewhat of a ubiquitous role in brain functioning, and is implicated in various diseases, including depression, stroke, Alzheimer's, and addictive disorders (Nagahara and Tuszynski, 2011; Biliński et al., 2012). Thus, evidence that ELS can trigger BDNF expression changes in adulthood has immense implications concerning vulnerability toward the development of these disorders. "
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ABSTRACT: Early life stress interacts with adult stress to differentially modulate neural systems and vulnerability to various psychiatric illnesses. However, the effects of early life stress and adult stress on addictive behaviors have not been sufficiently investigated. We examined the effects of early life stress in the form of prolonged maternal separation, followed in early adulthood by either 10 days of chronic variable stress or no stress, on methamphetamine self-administration, extinction, and cue-induced reinstatement. We observed that chronic variable stress in adulthood reduced methamphetamine self-administration in rats with a history of early life stress. These findings add to an emerging body of literature suggesting interactions between early life and early adulthood stressors on adult behavioral phenotypes.
Behavioural pharmacology 07/2015; DOI:10.1097/FBP.0000000000000166 · 2.15 Impact Factor
Available from: Jianmin Zhang
- "Our data showed that these two treatment groups exhibited no significant difference on stimulating TrkB phosphorylation 6 h following SAH, while the HIOC group showed improved neurobehavioral outcomes and exerted a tendency of activating TrkB more potently than the BDNF group 24 h post-SAH (Figs. 5, 6). It has been reported that BDNF has poor blood brain barrier penetrability and short serum half-life, and induces TrkB polyubiquitination and degradation, and these features made BDNF's clinical application problematic (Nagahara and Tuszynski, 2011; Shen et al., 2012). From this observation , it seems that HIOC, as a small compound, is more efficient and has prolonged effects on activating TrkB and its downstream effector than BDNF, thus a good candidate for future consideration. "
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ABSTRACT: N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC), an N-acetyl serotonin's derivative, selectively activates tropomyosin-related kinase receptor B (TrkB). This study is to investigate a potential role of HIOC on ameliorating early brain injury after experimental subarachnoid hemorrhage (SAH). One hundred and fifty-six adult male Sprague-Dawley rats were used. SAH model was induced by endovascular perforation. TrkB small interfering RNA (siRNA) or scramble siRNA was injected intracerebroventricularly 24hours before SAH. HIOC was administrated intracerebroventricularly 3hours after SAH and compared with brain-derived neurotrophic factor (BDNF). SAH grade and neurologic scores were evaluated for the outcome study. For the mechanism study, the expression of TrkB, phosphorylated TrkB (p-TrkB), phosphorylated extracellular signal regulated kinase (p-ERK), B-cell lymphoma 2 (Bcl-2) and cleaved caspase 3 (CC3) were detected by Western blots, and neuronal injury was determined by double immunofluorescence staining of neuronal nuclei and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling. Knocking down of TrkB decreased the expression of Bcl-2 and aggravated neurologic deficits 24hours after SAH. HIOC activated TrkB/ERK pathway, decreased neuronal cell death, improved neurobehavioral outcome, and these effects were abolished by TrkB siRNA. HIOC was more potent than BDNF in reduction of apoptosis 24hours post-SAH. Thus, we conclude that administration of HIOC activated TrkB/ERK signaling cascade and attenuated early brain injury after SAH. HIOC may be a promising agent for further treatment for SAH and other stroke events.
Copyright © 2015. Published by Elsevier Inc.
Neurobiology of Disease 04/2015; 78. DOI:10.1016/j.nbd.2015.01.009 · 5.08 Impact Factor
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