Post-transcriptional Regulation by Brain-Derived Neurotrophic Factor in the Nervous System
Brain-derived neurotrophic factor (BDNF) is a prominent regulator of activity-dependent neuronal gene expression. Through activation of Tropomyosin-related kinase B (TrkB) receptors, BDNF signaling promotes neuronal growth, survival, and plasticity by reg
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Alexandra M. Amen, Daniel L. Pham, and Mollie K. Meffert
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Introduction
Brain-derived neurotrophic factor (BDNF) is a secreted protein that belongs to the neurotrophin family of growth factors and influences the growth and survival of neurons in both the central and peripheral nervous systems. BDNF signaling is crucial in early development where it plays significant roles in neuronal progenitor proliferation and differentiation, cell survival, the outgrowth of neuronal processes, and both the formation and pruning of synaptic connections. Mice homozygous for loss of BDNF (BDNF knockout) often die post-natally, and surviving mice show significant nervous system dysfunction (Jones et al. 1994; Ernfors et al. 1995; Patterson et al. 1996). Additionally, throughout adulthood, secretion of BDNF in response to neuronal activity functions to promote synaptic strengthening and enhance learning and memory, as well as to provide general trophic support for neuronal health and survival. These critical roles mean that abnormal BDNF signaling is closely associated with a range of mental health disorders, including autism spectrum disorder, depression, schizophrenia, bipolar disorder, and anxiety disorders, as well as neurodegenerative diseases, including Alzheimer’s Disease and Parkinson’s Disease (McAllister et al. 1999; Muglia et al. 2002; Tyler et al. 2002; Zuccato and Cattaneo 2009; Santos et al. 2010; Nagahara and Tuszynski 2011; Andero and Ressler 2012).
A.M. Amen • D.L. Pham Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA M.K. Meffert (*) Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 K.M.J. Menon, A.C. Goldstrohm (eds.), Post-transcriptional Mechanisms in Endocrine Regulation, DOI 10.1007/978-3-319-25124-0_14
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BDNF expression is highest in the brain and is present in all brain regions, with the highest BDNF mRNA levels generally observed in the hippocampus and cerebral cortex (Wetmore et al. 1990; Conner et al. 1997). Despite its name, BDNF is also expressed and functional in a range of tissues outside the brain, including the peripheral nervous system, retina, skeletal muscle, kidneys, bone, and ovaries (Johnson et al. 1986; Jones et al. 1994; Ernfors et al. 1990; Griesbeck et al. 1995; Huber et al. 1996). In each of these tissues BDNF has been reported to play trophic roles in cell growth, survival, or repair (Fig. 14.1), but this chapter will focus particularly on BDNF in the central nervous system (CNS) where knowledge of downstream signaling events is the most comprehensive. BDNF has been well-characterized as a critical regulator of learning and memory in the hippocampus, and these studies have played a prominent role in elucidating the post-transcriptional m
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