Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain

2006 ◽  
Vol 34 (4) ◽  
pp. 600-604 ◽  
Author(s):  
J. Soulé ◽  
E. Messaoudi ◽  
C.R. Bramham
Keyword(s):  
Gene Expression ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Brain Derived Neurotrophic Factor ◽  
Adult Brain ◽  
Memory Storage ◽  
Early Gene ◽  
High Frequency Stimulation ◽  
Activity Dependent

Interest in BDNF (brain-derived neurotrophic factor) as an activity-dependent modulator of neuronal structure and function in the adult brain has intensified in recent years. Localization of BDNF and its receptor tyrosine kinase TrkB (tropomyosin receptor kinase B) to glutamate synapses makes this system attractive as a dynamic, activity-dependent regulator of excitatory transmission and synaptic plasticity in the adult brain. Development of stable LTP (long-term potentiation) in response to high-frequency stimulation requires new gene expression and protein synthesis, a process referred to as synaptic consolidation. Several lines of evidence have implicated endogenous BDNF–TrkB signalling in synaptic consolidation. This mini-review emphasizes new insights into the molecular mechanisms underlying this process. The immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is strongly induced and transported to dendritic processes after LTP induction in the dentate gyrus in live rats. Recent work suggests that sustained synthesis of Arc during a surprisingly protracted time-window is required for hyperphosphorylation of actin-depolymerizing factor/cofilin and local expansion of the actin cytoskeleton in vivo. Moreover, this process of Arc-dependent synaptic consolidation is activated in response to brief infusion of BDNF. Microarray expression profiling has also revealed a panel of BDNF-regulated genes that may co-operate with Arc during LTP maintenance. In addition to regulating gene expression, BDNF signalling modulates the fine localization and biochemical activation of the translation machinery. By modulating the spatial and temporal translation of newly induced (Arc) and constitutively expressed mRNA in neuronal dendrites, BDNF may effectively control the window of synaptic consolidation. These findings have implications for mechanisms of memory storage and mood control.

scholarly journals MAPK, CREB and zif268 are all required for the consolidation of recognition memory

2003 ◽  
Vol 358 (1432) ◽  
pp. 805-814 ◽  
Author(s):  
Bruno Bozon ◽  
Áine Kelly ◽  
Sheena A. Josselyn ◽  
Alcino J. Silva ◽  
Sabrina Davis ◽  
...  
Keyword(s):  
Recognition Memory ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Mitogen Activated Protein Kinase ◽  
Early Gene ◽  
Essential Components ◽  
And Storage

There has been nearly a century of interest in the idea that encoding and storage of information in the brain requires changes in the efficacy of synaptic connections between neurons that are activated during learning. Recent research into the molecular mechanisms of long-term potentiation (LTP) has brought about new knowledge that has provided valuable insights into the neural mechanisms of memory storage. The evidence indicates that rapid activation of the genetic machinery can be a key mechanism underlying the enduring modification of neural networks required for the stability of memories. In recent years, a wealth of experimental data has highlighted the importance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signalling in the regulation of gene transcription in neurons. Here, we briefly review experiments that have shown MAPK/ERK, cAMP response element-binding protein (CREB) and the immediate early gene (IEG) zif268 are essential components of a signalling cascade required for the expression of late phase LTP and of certain forms of long-term memory. We also present experiments in which we have assessed the role of these three molecules in recognition memory. We show that pharmacological blockade of MAPK/ERK phosphorylation, functional inactivation of CREB in an inducible transgenic mouse and inactivation of zif268 in a mutant mouse result in a similar deficit in long-term recognition memory. In the continuing debate about the role of LTP mechanisms in memory, these findings provide an important complement to the suggestion that synaptic changes brought about by LTP and memory consolidation and storage share, at least in part, common underlying molecular mechanisms.

scholarly journals Brain-Derived Neurotrophic Factor and Its Potential Therapeutic Role in Stroke Comorbidities

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Wei Liu ◽  
Xiaohui Wang ◽  
Margaret O’Connor ◽  
Guan Wang ◽  
Fang Han
Keyword(s):  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Brain Derived Neurotrophic Factor ◽  
Therapeutic Strategies ◽  
Adult Brain ◽  
Human Society ◽  
Potential Therapeutic Role ◽  
To Receive ◽  
The Brain ◽  
Global Population

With the rise in the aging global population, stroke comorbidities have become a serious health threat and a tremendous economic burden on human society. Current therapeutic strategies mainly focus on protecting neurons from cytotoxic damage at the acute phase upon stroke onset, which not only is a difficult way to ameliorate stroke symptoms but also presents a challenge for the patients to receive effective treatment in time. The brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the adult brain, which possesses a remarkable capability to repair brain damage. Recent promising preclinical outcomes have made BDNF a popular late-stage target in the development of novel stroke treatments. In this review, we aim to summarize the latest progress in the understanding of the cellular/molecular mechanisms underlying stroke pathogenesis, current strategies and difficulties in drug development, the mechanism of BDNF action in poststroke neurorehabilitation and neuroplasticity, and recent updates in novel therapeutic methods.

Brain-Derived Neurotrophic Factor Systemic Response in the Periodontium, Trigeminal Nucleus Caudalis, and Hippocampus Induced by Occlusal Trauma

2021 ◽  
Vol 17 (7) ◽  
pp. 1371-1379
Author(s):  
Di Liu ◽  
Ying Li ◽  
Jiechen Liu ◽  
Zhiyuan Shen ◽  
Fengying Wang ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Systemic Response ◽  
Periodontal Tissue ◽  
Trigeminal Nucleus ◽  
Bdnf Gene ◽  
Dental Tissue ◽  
Injury And Repair ◽  
Activity Dependent ◽  
The Brain

Occlusal trauma (OT), by causing periodontal tissue damage, can activate and enhance the activity of the peripheral and central nervous system (CNS) neuropeptides. The brain-derived neurotrophic factor (BDNF) gene is activity-dependent and exhibits marked alterations, characterized by protection against injury and repair. Our results show the possible molecular mechanism through which noxious environmental stimuli induce alterations in BDNF activity in the local periodontal tissue, the primary sensory neurons-Vc, and the hippocampus, suggesting systemic impairment. BDNF serves a more positive and enduring trauma protection and repair function in Vc compared to that in local dental tissue.

scholarly journals Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson's disease

2017 ◽  
Vol 1 (2) ◽  
Author(s):  
Gerard W. O'Keeffe ◽  
Shane V. Hegarty ◽  
Aideen M. Sullivan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Axon Growth ◽  
Nervous System Development ◽  
Adult Brain ◽  
Bmp Receptors

Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by the degeneration of midbrain dopaminergic (mDA) neurons and their axons, and aggregation of α-synuclein, which leads to motor and late-stage cognitive impairments. As the motor symptoms of PD are caused by the degeneration of a specific population of mDA neurons, PD lends itself to neurotrophic factor therapy. The goal of this therapy is to apply a neurotrophic factor that can slow down, halt or even reverse the progressive degeneration of mDA neurons. While the best known neurotrophic factors are members of the glial cell line-derived neurotrophic factor (GDNF) family, their lack of clinical efficacy to date means that it is important to continue to study other neurotrophic factors. Bone morphogenetic proteins (BMPs) are naturally secreted proteins that play critical roles during nervous system development and in the adult brain. In this review, we provide an overview of the BMP ligands, BMP receptors (BMPRs) and their intracellular signalling effectors, the Smad proteins. We review the available evidence that BMP–Smad signalling pathways play an endogenous role in mDA neuronal survival in vivo, before outlining how exogenous application of BMPs exerts potent effects on mDA neuron survival and axon growth in vitro and in vivo. We discuss the molecular mechanisms that mediate these effects, before highlighting the potential of targeting the downstream effectors of BMP–Smad signalling as a novel neuroprotective approach to slow or stop the degeneration of mDA neurons in PD.

scholarly journals Cellular and molecular mechanisms regulating neuronal growth by brain-derived neurotrophic factor

Cytoskeleton ◽  
2016 ◽  
Vol 73 (10) ◽  
pp. 612-628 ◽  
Author(s):  
Andres Gonzalez ◽  
Guillermo Moya-Alvarado ◽  
Christian Gonzalez-Billaut ◽  
Francisca C. Bronfman
Keyword(s):  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Brain Derived Neurotrophic Factor ◽  
Neuronal Growth
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