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Role of Brain-Derived Neurotrophic Factor as a Modulator of Synaptic Plasticity

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Brain Aging and Therapeutic Interventions

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Abstract

Brain-derived neurotrophic factor (BDNF) is one of the most active members of the neurotrophin family. BDNF not only regulates neuronal survival and differentiation, but also functions in activity-dependent plasticity processes such as long-term potentiation (LTP), long-term depression (LTD), learning and memory. BDNF is synthesized as a precursor protein (proBDNF) that is proteolytically cleaved to form the mature protein. BDNF mediates its effects via two distinct receptors: the high-affinity tropomyosin-related kinase B (TrkB) receptor, which displays specificity for BDNF and other neurotrophin family members (e.g., neurotrophin-4/5 (NT-4/5)), and the low-affinity p75 neurotrophin receptor (p75NTR), which binds to BDNF, neurotrophin-3 (NT-3), NT-4/5, and nerve growth factor (NGF). This review addresses various roles of BDNF in neuronal activity, with special emphasis on its role in mechanisms of activity-dependent synaptic plasticity. Activity-dependent synaptic plasticity, as exemplified by LTP and LTD, is widely accepted as the cellular correlate of learning and memory. LTP and LTD, each requires input specificity and occurs in two temporally distinct phases: early-LTP/LTD (E-LTP/LTD) and late-LTP/LTD (L-LTP/LTD). L-LTP and L-LTD persist for many hours and require new protein synthesis. This review discusses the impact of BDNF on translation-dependent synaptic plasticity. Increasing data indicate that the function of BDNF in synaptic plasticity requires a tight relationship between extracellular neurotrophin release, synaptic activity-dependent local protein synthesis, and BDNF polymorphism. This article also addresses the cellular and molecular mechanisms underlying the functional changes of hippocampal synapses during neuronal plasticity, including our findings in regard to the post-translational processing of proBDNF.

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Acknowledgements

This work was supported by the Core Research for Evolutional Science and Technology (CREST) program of the Japan Science and Technology Agency (JST).

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Authors and Affiliations

  1. Laboratory of Functional Neuroscience, Nara Institute of Science and Technology, 8916-5, Takayama,, 630-0192, Ikoma, Nara, Japan

    Yasuyuki Ishikawa

  2. Bio-interface Research Group, Health Research Inst., National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorioka,, 563-8577, Ikeda, Osaka, Japan

    Masami Kojima

  3. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, 332-0012, Kawaguchi, Japan

    Yasuyuki Ishikawa & Masami Kojima

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  1. Yasuyuki Ishikawa
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  2. Masami Kojima
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Correspondence to Masami Kojima .

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  1. , Department of Zoology, Banaras Hindu University, Varanasi, 221005, India

    Mahendra K. Thakur

  2. , Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10-C, Aarhus-C, 8000, Denmark

    Suresh I.S. Rattan

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Ishikawa, Y., Kojima, M. (2012). Role of Brain-Derived Neurotrophic Factor as a Modulator of Synaptic Plasticity. In: Thakur, M., Rattan, S. (eds) Brain Aging and Therapeutic Interventions. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5237-5_3

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