Ji Y, Lu Y, Yang F, Shen W, Tang TT, Feng L et al. Acute and gradual increases in BDNF concentration elicit distinct signaling and functions in neurons. Nat Neurosci 13: 302-309

Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Nature Neuroscience (Impact Factor: 16.1). 02/2010; 13(3):302-9. DOI: 10.1038/nn.2505
Source: PubMed


Extracellular factors may act on cells in two distinct modes: an acute increase in concentration as a result of regulated secretion, or a gradual increase in concentration when secreted constitutively or from a distant source. We found that cellular responses to brain-derived neurotrophic factor (BDNF) differed markedly depending on how BDNF was delivered. In cultured rat hippocampal neurons, acute and gradual increases in BDNF elicited transient and sustained activation of TrkB receptor and its downstream signaling, respectively, leading to differential expression of Homer1 and Arc. Transient TrkB activation promoted neurite elongation and spine head enlargement, whereas sustained TrkB activation facilitated neurite branch and spine neck elongation. In hippocampal slices, fast and slow increases in BDNF enhanced basal synaptic transmission and LTP, respectively. Thus, the kinetics of TrkB activation is critical for cell signaling and functions. This temporal dimension in cellular signaling may also have implications for the therapeutic drug design.

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Available from: Wanhua Shen, Jan 13, 2016
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    • "Treatment of neurons with recombinant progranulin was shown to increase synapse density, while decreasing the size of the presynaptic compartment and specifically the number of synaptic vesicles per synapse (Petoukhov et al., 2013). In parallel, a study has demonstrated that acute and gradual increases in BDNF concentration activate different intracellular cascades, leading to differences in spine morphology (Ji et al., 2010). These results suggest that it is not only the concentration of secreted BDNF that it is important for the regulation of neuronal function and morphology, but also the manner in which it is secreted: constitutively or in response to neuronal activity. "
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    • "Dendrites and spines were traced and marked manually in a three-dimensional space. The loss or gain rate of dendritic spines was calculated as the percentage of spines that appeared or disappeared on day 1, relative to the total number of spines on day 0. The length of spines was measured from the tip of the spine to the interface with the dendritic stalk (Ji et al., 2010 "
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    • "BDNF enhances the expression and trafficking of GluN2A in cultured cortical and hippocampal neurons, and induces the phosphorylation of GluN2A subunit in PSD of rat spinal cord (Di et al., 2001; Hayashi et al., 2000), which is associated with an increase in NMDA receptor activity (Caldeira et al., 2007b; Small et al., 1998), whereas absence of BDNF induces a reduction of GluN2A level in the visual cortex of BDNF knock-out mice (Margottil and Domenici, 2003). Involvement of GluN2A-containing NMDA (GluN2A-NMDA) receptor in the development of LTP is supported by the findings that pharmacological inhibition of GluN2A by NVP-AAM077 blocks the induction of LTP in multiple brain regions including the hippocampus (Bartlett et al., 2007; Fox et al., 2006; Jin and Feig, 2010; Li et al., 2007; Liu et al., 2004; Volianskis et al., 2013), the cortex (Massey et al., 2004) as well as the amygdala (Dalton et al., 2012; Muller et al., 2009) and the nucleus accumbens (Schotanus and Chergui, 2008). Deletion of GluN2A subunit in mice results in a impaired induction of postsynaptic LTP in the dentate gyrus (Kannangara et al., 2014) and the visual cortex (Philpot et al., 2007), and at the mossy fiber to granule cell synapse in the cerebellum (Andreescu et al., 2011). "
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