Neurotrophin regulation of neural circuit development and function
TL;DR: Some of the recent progress in understanding the cellular and molecular mechanisms underlying neurotrophin regulation of neural circuits are summarized in this Review.
Abstract: Brain-derived neurotrophic factor (BDNF)--a member of a small family of secreted proteins that includes nerve growth factor, neurotrophin 3 and neurotrophin 4--has emerged as a key regulator of neural circuit development and function. The expression, secretion and actions of BDNF are directly controlled by neural activity, and secreted BDNF is capable of mediating many activity-dependent processes in the mammalian brain, including neuronal differentiation and growth, synapse formation and plasticity, and higher cognitive functions. This Review summarizes some of the recent progress in understanding the cellular and molecular mechanisms underlying neurotrophin regulation of neural circuits. The focus of the article is on BDNF, as this is the most widely expressed and studied neurotrophin in the mammalian brain.
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TL;DR: It is shown that FNDC5, a previously identified muscle protein that is induced in exercise and is cleaved and secreted as irisin, is also elevated by endurance exercise in the hippocampus of mice.
868 citations
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...BDNF promotes many aspects of brain development, including neuronal cell survival, differentiation, migration, dendritic arborization, synaptogenesis, and plasticity (Greenberg et al., 2009; Park and Poo, 2013)....
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TL;DR: The biological intersection of neurodevelopment and the microbiome is discussed and the hypothesis that gut bacteria are integral contributors to development and function of the nervous system and the balance between mental health and disease is explored.
862 citations
Cites background from "Neurotrophin regulation of neural c..."
...Mounting evidence suggests that the communication between the brain and gut microbial populations is bi-directional (Bailey et al., 2011; Carabotti et al., 2015; Moussaoui et al., 2014; Park et al., 2013)....
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TL;DR: The importance of BDNF for future studies aimed at disclosing mechanisms of activation of signaling pathways, neuro- and gliogenesis, as well as synaptic plasticity is highlighted.
Abstract: Brain-derived neurotrophic factor (BDNF) is one of the most widely distributed and extensively studied neurotrophins in the mammalian brain. Among its prominent functions, one can mention control of neuronal and glial development, neuroprotection, and modulation of both short- and long-lasting synaptic interactions, which are critical for cognition and memory. A wide spectrum of processes are controlled by BDNF, and the sometimes contradictory effects of its action can be explained based on its specific pattern of synthesis, comprising several intermediate biologically active isoforms that bind to different types of receptor, triggering several signaling pathways. The functions of BDNF must be discussed in close relation to the stage of brain development, the different cellular components of nervous tissue, as well as the molecular mechanisms of signal transduction activated under physiological and pathological conditions. In this review, we briefly summarize the current state of knowledge regarding the impact of BDNF on regulation of neurophysiological processes. The importance of BDNF for future studies aimed at disclosing mechanisms of activation of signaling pathways, neuro- and gliogenesis, as well as synaptic plasticity is highlighted.
715 citations
Cites background from "Neurotrophin regulation of neural c..."
...The BDNF- controlled long-lasting effects of LTP and alterations in the synaptic proteome may result from modulation of micro- RNA (miRNA) expression (Jaitner et al. 2016; Leal et al. 2014; Smalheiser et al. 2010)....
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...ergic interneurons, together enhancing hippocampal longterm potentiation (LTP) (Leal et al. 2015; Park and Poo 2013)....
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...The presynaptic effect of BDNF on hippocampal LTP has been reported in Schaffer’s collaterals (Zakharenko et al. 2003)....
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...The PI3K/Akt-related pathway exerts antiapoptotic and prosurvival activity and modulates N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity (Baydyuk and Xu 2014; Gonzalez et al. 2016; Park and Poo 2013)....
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...Due to the reduction in the number of neurons and deterioration of synaptic function, these processes contribute to longterm depression (LTD), as revealed in hippocampal neurons (Park and Poo 2013; Woo et al. 2005; Yang et al. 2014)....
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TL;DR: This review aims at highlighting photochemical transformations as a tool for rapidly accessing structurally and stereochemically diverse scaffolds for complex polycyclic carbon skeletons with impressive efficiency, which are of high value in total synthesis.
Abstract: The use of photochemical transformations is a powerful strategy that allows for the formation of a high degree of molecular complexity from relatively simple building blocks in a single step. A central feature of all light-promoted transformations is the involvement of electronically excited states, generated upon absorption of photons. This produces transient reactive intermediates and significantly alters the reactivity of a chemical compound. The input of energy provided by light thus offers a means to produce strained and unique target compounds that cannot be assembled using thermal protocols. This review aims at highlighting photochemical transformations as a tool for rapidly accessing structurally and stereochemically diverse scaffolds. Synthetic designs based on photochemical transformations have the potential to afford complex polycyclic carbon skeletons with impressive efficiency, which are of high value in total synthesis.
692 citations
TL;DR: Current data suggests that conventional antidepressants and ketamine mediate their antidepressant-like effects by increasing BDNF in forebrain regions, in particular the hippocampus, making BDNF an essential determinant of antidepressant efficacy.
630 citations
References
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TL;DR: A role is demonstrated for BDNF and its val/met polymorphism in human memory and hippocampal function and it is suggested val/ met exerts these effects by impacting intracellular trafficking and activity-dependent secretion of BDNF.
3,599 citations
TL;DR: The field of experimental embryology, which had been enthusiastically acclaimed in the mid-thirties, suffered from a sharp decrease in the enthusiasm that had inflamed the pioneers in this field, ever since R. G. Harrison delivered his celebrated lecture at the Royal Society in London in 1935.
Abstract: "Embryogenesis is in some way a model system. It has always been distinguished by the exactitude even punctitio, of its anatomical descriptions. An experiment by one of the great masters of embryology could be made the text of a discourse on scientific method. But something is wrong, or has been wrong. There is no theory of development in the sense in which Mendelism is a theory that accounts for the results of breeding experiments. There has therefore been little sense of progression or timeliness about embryological research. Of many papers delivered at embryological meetings, however good they may be in themselves . . . one too often feels that they might have been delivered five years beforehand without making anyone much the wiser, or deferred for five years without making anyone conscious of a great loss" (1). This feeling of frustration so incisively conveyed by these considerations by P. Medawar, pervaded, in the forties, the field of experimental embryology which had been enthusiastically acclaimed in the mid-thirties, when the upper lip of the amphibian blastopore brought this area of research to the forefront of the biological stage. The side branch of experimental neuroembryology, which had stemmed out from the common tree and was entirely devoted to the study of the tropic interrelations between neuronal cell populations and between these and the innervated organs and tissues, was then in its initial vigorous growth phase. It in turn suffered from a sharp decrease in the enthusiasm that had inflamed the pioneers in this field, ever since R. G. Harrison delivered his celebrated lecture on this topic at the Royal Society in London in 1935 (2). Although the alternate "wax and wane" cycles are the rule rather than the exception in all fields of human endeavor, in that of biological sciences the "wane" is all too often indicative of a justified loss of faith in the rational and methodical approach that had at first raised so much hope. A brief account of the state-of-the-art of experimental neuroembryology in the
3,061 citations
"Neurotrophin regulation of neural c..." refers background in this paper
...mitogen-activated protein kinase (MAPK) phosphorylation of synapsin (2), and RAB3 expression (3), leading to increased...
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TL;DR: The sequential combination of spontaneously generated and experience-dependent neural activity endows the brain with an ongoing ability to accommodate to dynamically changing inputs during development and throughout life.
Abstract: Vision is critical for the functional and structural maturation of connections in the mammalian visual system. Visual experience, however, is a subset of a more general requirement for neural activity in transforming immature circuits into the organized connections that subserve adult brain function. Early in development, internally generated spontaneous activity sculpts circuits on the basis of the brain's "best guess" at the initial configuration of connections necessary for function and survival. With maturation of the sense organs, the developing brain relies less on spontaneous activity and increasingly on sensory experience. The sequential combination of spontaneously generated and experience-dependent neural activity endows the brain with an ongoing ability to accommodate to dynamically changing inputs during development and throughout life.
2,880 citations
TL;DR: Recent findings that neurotrophins, in addition to promoting survival and differentiation, exert various effects through surprising interactions with other receptors and ion channels are reviewed.
Abstract: The neurotrophins are a family of proteins that are essential for the development of the vertebrate nervous system. Each neurotrophin can signal through two different types of cell surface receptor — the Trk receptor tyrosine kinases and the p75 neurotrophin receptor. Given the wide range of activities that are now associated with neurotrophins, it is probable that additional regulatory events and signalling systems are involved. Here, I review recent findings that neurotrophins, in addition to promoting survival and differentiation, exert various effects through surprising interactions with other receptors and ion channels.
2,065 citations
"Neurotrophin regulation of neural c..." refers background in this paper
...(AMPAR) subunits and increase their synaptic delivery (6)....
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TL;DR: Rapid actions of neurotrophin-3 on synaptic efficacy, as well as the regulation of their mRNAs by electrical activity, suggest that neurotrophins might play important roles in regulating neuronal connectivity in the developing and in the adult central nervous system.
Abstract: The neurotrophins are a small group of dimeric proteins that profoundly affect the development of the nervous system of vertebrates. Recent studies have established clear correlations between the survival requirements for different neurotrophins of functionally distinct subsets of sensory neurons. The biological role of the neurotrophins is not limited to the prevention of programmed cell death of specific groups of neurons during development. Neurotrophin-3 in particular seems to act on neurons well before the period of target innervation and of normally occuning cell death. In animals lacking functional neurotrophin or receptor genes, neuronal numbers do not seem to be massively reduced in the CNS, unlike in the PNS. Finally, rapid actions of neurotrophins on synaptic efficacy, as well as the regulation of their mRNAs by electrical activity, suggest that neurotrophins might play important roles in regulating neuronal connectivity in the developing and in the adult central nervous system.
1,969 citations
"Neurotrophin regulation of neural c..." refers background in this paper
...On the postsynaptic side, TRK signalling causes tyrosine phosphorylation of voltage-gated Na (Na V ) and voltage-gated K (K V ) channels and NMDA-type glutamate receptor (NMDAR) subunits, modifying the conductance of all these channels (5)....
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