BDNF signaling during the lifetime of dendritic spines

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Abstract

Dendritic spines are tiny membrane specialization forming the postsynaptic part of most excitatory synapses. They have been suggested to play a crucial role in regulating synaptic transmission during development and in adult learning processes. Changes in their number, size, and shape are correlated with processes of structural synaptic plasticity and learning and memory and also with neurodegenerative diseases, when spines are lost. Thus, their alterations can correlate with neuronal homeostasis, but also with dysfunction in several neurological disorders characterized by cognitive impairment. Therefore, it is important to understand how different stages in the life of a dendritic spine, including formation, maturation, and plasticity, are strictly regulated. In this context, brain-derived neurotrophic factor (BDNF), belonging to the NGF-neurotrophin family, is among the most intensively investigated molecule. This review would like to report the current knowledge regarding the role of BDNF in regulating dendritic spine number, structure, and plasticity concentrating especially on its signaling via its two often functionally antagonistic receptors, TrkB and p75 ^NTR. In addition, we point out a series of open points in which, while the role of BDNF signaling is extremely likely conclusive, evidence is still missing.

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Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor.

Christopher N. Parkhurst, Guang. Yang, Ipe Ninan … (2013)

Microglia are the resident macrophages of the CNS, and their functions have been extensively studied in various brain pathologies. The physiological roles of microglia in brain plasticity and function, however, remain unclear. To address this question, we generated CX3CR1(CreER) mice expressing tamoxifen-inducible Cre recombinase that allow for specific manipulation of gene function in microglia. Using CX3CR1(CreER) to drive diphtheria toxin receptor expression in microglia, we found that microglia could be specifically depleted from the brain upon diphtheria toxin administration. Mice depleted of microglia showed deficits in multiple learning tasks and a significant reduction in motor-learning-dependent synapse formation. Furthermore, Cre-dependent removal of brain-derived neurotrophic factor (BDNF) from microglia largely recapitulated the effects of microglia depletion. Microglial BDNF increases neuronal tropomyosin-related kinase receptor B phosphorylation, a key mediator of synaptic plasticity. Together, our findings reveal that microglia serve important physiological functions in learning and memory by promoting learning-related synapse formation through BDNF signaling. Copyright © 2013 Elsevier Inc. All rights reserved.

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Neurotrophin regulation of neural circuit development and function.

Hyungju Park, Mu-ming Poo (2013)

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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Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments

Ronald S. Duman, Gerard Sanacora, John Krystal (2019)

The mechanisms underlying the pathophysiology and treatment of depression and stress-related disorders remain unclear, but studies in depressed patients and rodent models are beginning to yield promising insights. These studies demonstrate that depression and chronic stress exposure cause atrophy of neurons in cortical and limbic brain regions implicated in depression, and brain imaging studies demonstrate altered connectivity and network function in the brains of depressed patients. Studies of the neurobiological basis of the these alterations have focused on both the principle, excitatory glutamate neurons, as well as inhibitory GABA interneurons. They demonstrate structural, functional, and neurochemical deficits in both major neuronal types that could lead to degradation of signal integrity in cortical and hippocampal regions. The molecular mechanisms underlying these changes have not been identified but are thought to be related to stress induced excitotoxic effects in combination with elevated adrenal glucocorticoids and inflammatory cytokines, (as well as other environmental factors). Transcriptomic studies are beginning to demonstrate important sex differences and together with genomic studies are starting to reveal mechanistic domains of overlap and uniqueness with regards to risk and pathophysiological mechanisms with schizophrenia and bipolar disorder. These studies also implicate GABA and glutamate dysfunction as well as immunologic mechanisms. While current antidepressants have significant time lag and efficacy limitations, new, rapid acting agents that target the glutamate and GABA systems address these issues and offer superior therapeutic interventions for this widespread and debilitating disorder. The review by Duman and colleagues discusses evidence that depression is characterized by deficits of excitatory and inhibitory neurons, while new rapid acting agents that target the glutamate and GABA systems address these issues and offer superior therapeutic interventions.

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Author and article information

Contributors

Marta Zagrebelsky: m.zagrebelsky@tu-bs.de

Martin Korte:

ORCID: http://orcid.org/0000-0001-6956-5913

m.korte@tu-bs.de

Journal

Journal ID (nlm-ta): Cell Tissue Res

Journal ID (iso-abbrev): Cell Tissue Res

Title: Cell and Tissue Research

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0302-766X

ISSN (Electronic): 1432-0878

Publication date (Electronic): 14 June 2020

Publication date PMC-release: 14 June 2020

Publication date (Print): 2020

Volume: 382

Issue: 1

Pages: 185-199

Affiliations

[1 ]GRID grid.6738.a, ISNI 0000 0001 1090 0254, Division of Cellular Neurobiology, Zoological Institute, , TU Braunschweig, ; Spielmannstr 7, 38106 Braunschweig, Germany

[2 ]GRID grid.7490.a, ISNI 0000 0001 2238 295X, Helmholtz Centre for Infection Research, AG NIND, ; Inhoffenstr. 7, D-38124 Braunschweig, Germany

Author information

Martin Korte http://orcid.org/0000-0001-6956-5913

Article

Publisher ID: 3226

DOI: 10.1007/s00441-020-03226-5

PMC ID: 7529616

PubMed ID: 32537724

SO-VID: 7c056c21-70cf-42ee-b53e-a903d31cd2cf

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 28 February 2020

Date accepted : 27 April 2020

Funding

Funded by: DFG

Award ID: DFG grant KO 1674/5-1

Award Recipient : Martin Korte

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ScienceOpen disciplines: Molecular medicine

Keywords: brain-derived neurotrophic factor,dendritic spines,neurotrophin,trkb,p75ntr

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ScienceOpen disciplines: Molecular medicine

Keywords: brain-derived neurotrophic factor, dendritic spines, neurotrophin, trkb, p75ntr

BDNF signaling during the lifetime of dendritic spines

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Abstract

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Neuronal Signaling

Most cited references 186

Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor.

Neurotrophin regulation of neural circuit development and function.

Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments

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