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      Brain-derived neurotrophic factor and its clinical implications

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          Abstract

          Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduction cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BDNF and insulin-like growth factor-1 have similar downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression of pro-survival genes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents exhaustion of β cells. Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.

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          BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis.

          Clive Bramham, Elhoucine Messaoudi (2005)
          Interest in BDNF as an activity-dependent modulator of neuronal structure and function in the adult brain has intensified in recent years. Localization of BDNF-TrkB to glutamate synapses makes this system attractive as a dynamic, activity-dependent regulator of excitatory transmission and plasticity. Despite individual breakthroughs, an integrated understanding of BDNF function in synaptic plasticity is lacking. Here, we attempt to distill current knowledge of the molecular mechanisms and function of BDNF in LTP. BDNF activates distinct mechanisms to regulate the induction, early maintenance, and late maintenance phases of LTP. Evidence from genetic and pharmacological approaches is reviewed and tabulated. The specific contribution of BDNF depends on the stimulus pattern used to induce LTP, which impacts the duration and perhaps the subcellular site of BDNF release. Particular attention is given to the role of BDNF as a trigger for protein synthesis-dependent late phase LTP--a process referred to as synaptic consolidation. Recent experiments suggest that BDNF activates synaptic consolidation through transcription and rapid dendritic trafficking of mRNA encoded by the immediate early gene, Arc. A model is proposed in which BDNF signaling at glutamate synapses drives the translation of newly transported (Arc) and locally stored (i.e., alphaCaMKII) mRNA in dendrites. In this model BDNF tags synapses for mRNA capture, while Arc translation defines a critical window for synaptic consolidation. The biochemical mechanisms by which BDNF regulates local translation are also discussed. Elucidation of these mechanisms should shed light on a range of adaptive brain responses including memory and mood resilience.
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            Brain-derived neurotrophic factor.

            Devin K Binder, Helen Scharfman (2004)
            Since the purification of BDNF in 1982, a great deal of evidence has mounted for its central roles in brain development, physiology, and pathology. Aside from its importance in neural development and cell survival, BDNF appears essential to molecular mechanisms of synaptic plasticity. Basic activity-related changes in the central nervous system are thought to depend on BDNF modification of synaptic transmission, especially in the hippocampus and neocortex. Pathologic levels of BDNF-dependent synaptic plasticity may contribute to conditions such as epilepsy and chronic pain sensitization, whereas application of the trophic properties of BDNF may lead to novel therapeutic options in neurodegenerative diseases and perhaps even in neuropsychiatric disorders.
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              Exercise and brain neurotrophins.

              S A Neeper, F Gómez-Pinilla, J. Choi … (1995)
              Article 0 comments Cited 255 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Arch Med Sci
                Journal ID (iso-abbrev): Arch Med Sci
                Journal ID (publisher-id): AMS
                Title: Archives of Medical Science : AMS
                Publisher: Termedia Publishing House
                ISSN (Print): 1734-1922
                ISSN (Electronic): 1896-9151
                Publication date (Electronic): 11 December 2015
                Publication date (Print): 10 December 2015
                Volume: 11
                Issue: 6
                Pages: 1164-1178
                Affiliations
                [1 ]Bio-Science Research Center, Gayatri Vidya Parishad College of Engineering, Visakhapatnam, India
                [2 ]UND Life Sciences, USA
                Author notes
                Corresponding author: Dr. Undurti N. Das MD, FAMS, FRSC, UND Life Sciences, 2020 S360th St, #K-202, Federal Way, WA 98003, USA. Phone: 216-231-5548. E-mail: undurti@ 123456hotmail.com
                Article
                Publisher ID: 26363
                DOI: 10.5114/aoms.2015.56342
                PMC ID: 4697050
                PubMed ID: 26788077
                SO-VID: 58014b12-7ede-4679-bfe7-1b08f95f4ec3
                Copyright © Copyright © 2015 Termedia & Banach
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                History
                Date received : 21 July 2014
                Date accepted : 05 August 2014
                Categories
                Subject: State of the Art Paper

                ScienceOpen disciplines: Medicine
                Keywords: brain-derived neurotrophic factor,β cell,signal transduction,diabetes mellitus,alzheimer's disease,neurotransmission
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: brain-derived neurotrophic factor, β cell, signal transduction, diabetes mellitus, alzheimer's disease, neurotransmission

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