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

Cellular and molecular mechanisms of the brain-derived neurotrophic factor in physiological and pathological conditions

2016 ◽  
Vol 131 (2) ◽  
pp. 123-138 ◽  
Author(s):  
Veronica Begni ◽  
Marco Andrea Riva ◽  
Annamaria Cattaneo
Keyword(s):  
Synaptic Plasticity ◽  
Stress Response ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Depressive Disorders ◽  
Brain Derived Neurotrophic Factor ◽  
Mitogen Activated Protein Kinase ◽  
Bdnf Expression ◽  
Pathological Conditions ◽  
Wide Range

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in the central nervous system, promoting synaptic plasticity, neurogenesis and neuroprotection. The BDNF gene structure is very complex and consists of multiple 5′-non-coding exons, which give rise to differently spliced transcripts, and one coding exon at the 3′-end. These multiple transcripts, together with the complex transcriptional regulatory machinery, lead to a complex and fine regulation of BDNF expression that can be tissue and stimulus specific. BDNF effects are mainly mediated by the high-affinity, tropomyosin-related, kinase B receptor and involve the activation of several downstream cascades, including the mitogen-activated protein kinase, phospholipase C-γ and phosphoinositide-3-kinase pathways. BDNF exerts a wide range of effects on neuronal function, including the modulation of activity-dependent synaptic plasticity and neurogenesis. Importantly, alterations in BDNF expression and function are involved in different brain disorders and represent a major downstream mechanism for stress response, which has important implications in psychiatric diseases, such as major depressive disorders and schizophrenia. In the present review, we have summarized the main features of BDNF in relation to neuronal plasticity, stress response and pathological conditions, and discussed the role of BDNF as a possible target for pharmacological and non-pharmacological treatments in the context of psychiatric illnesses.

The role of brain-derived neurotrophic factor and the neurotrophin receptor p75NTR in age-related brain atrophy and the transition to Alzheimer’s disease

2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Shaun Cade ◽  
Xin-Fu Zhou ◽  
Larisa Bobrovskaya
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Brain Derived Neurotrophic Factor ◽  
Neurotrophin Receptor ◽  
Current Evidence ◽  
Synaptic Dysfunction ◽  
Age Related

Abstract Alzheimer’s disease is a neurodegenerative condition that is potentially mediated by synaptic dysfunction before the onset of cognitive impairments. The disease mostly affects elderly people and there is currently no therapeutic which halts its progression. One therapeutic strategy for Alzheimer’s disease is to regenerate lost synapses by targeting mechanisms involved in synaptic plasticity. This strategy has led to promising drug candidates in clinical trials, but further progress needs to be made. An unresolved problem of Alzheimer’s disease is to identify the molecular mechanisms that render the aged brain susceptible to synaptic dysfunction. Understanding this susceptibility may identify drug targets which could halt, or even reverse, the disease’s progression. Brain derived neurotrophic factor is a neurotrophin expressed in the brain previously implicated in Alzheimer’s disease due to its involvement in synaptic plasticity. Low levels of the protein increase susceptibility to the disease and post-mortem studies consistently show reductions in its expression. A desirable therapeutic approach for Alzheimer’s disease is to stimulate the expression of brain derived neurotrophic factor and potentially regenerate lost synapses. However, synthesis and secretion of the protein are regulated by complex activity-dependent mechanisms within neurons, which makes this approach challenging. Moreover, the protein is synthesised as a precursor which exerts the opposite effect of its mature form through the neurotrophin receptor p75NTR. This review will evaluate current evidence on how age-related alterations in the synthesis, processing and signalling of brain derived neurotrophic factor may increase the risk of Alzheimer’s disease.

Molecular mechanisms of brain-derived neurotrophic factor in neuro-protection: Recent developments

2017 ◽  
Vol 1665 ◽  
pp. 1-21 ◽  
Author(s):  
Hailin Zhao ◽  
Azeem Alam ◽  
Chun-Yin San ◽  
Shiori Eguchi ◽  
Qian Chen ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Brain Derived Neurotrophic Factor ◽  
Recent Developments ◽  
Neuro Protection

scholarly journals Brain-Derived Neurotrophic Factor in Central Nervous System Myelination: A New Mechanism to Promote Myelin Plasticity and Repair

2018 ◽  
Vol 19 (12) ◽  
pp. 4131 ◽  
Author(s):  
Jessica Fletcher ◽  
Simon Murray ◽  
Junhua Xiao
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neural Development ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Demyelinating Disease ◽  
Cell Types ◽  
Brain Derived Neurotrophic Factor ◽  
Future Research ◽  
Health And Disease

Brain-derived neurotrophic factor (BDNF) plays vitally important roles in neural development and plasticity in both health and disease. Recent studies using mutant mice to selectively manipulate BDNF signalling in desired cell types, in combination with animal models of demyelinating disease, have demonstrated that BDNF not only potentiates normal central nervous system myelination in development but enhances recovery after myelin injury. However, the precise mechanisms by which BDNF enhances myelination in development and repair are unclear. Here, we review some of the recent progress made in understanding the influence BDNF exerts upon the myelinating process during development and after injury, and discuss the cellular and molecular mechanisms underlying its effects. In doing so, we raise new questions for future research.

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 Decreased Serum Brain-Derived Neurotrophic Factor (BDNF) Levels in Patients with Alzheimer’s Disease (AD): A Systematic Review and Meta-Analysis

2019 ◽  
Vol 20 (2) ◽  
pp. 257 ◽  
Author(s):  
Ted Ng ◽  
Cyrus Ho ◽  
Wilson Tam ◽  
Ee Kua ◽  
Roger Ho
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Meta Analysis ◽  
Brain Derived Neurotrophic Factor ◽  
Significant Heterogeneity ◽  
Healthy Controls ◽  
Healthy Control ◽  
Serum Bdnf

Findings from previous studies reporting the levels of serum brain-derived neurotrophic factor (BDNF) in patients with Alzheimer’s disease (AD) and individuals with mild cognitive impairment (MCI) have been conflicting. Hence, we performed a meta-analysis to examine the aggregate levels of serum BDNF in patients with AD and individuals with MCI, in comparison with healthy controls. Fifteen studies were included for the comparison between AD and healthy control (HC) (n = 2067). Serum BDNF levels were significantly lower in patients with AD (SMD: −0.282; 95% confidence interval [CI]: −0.535 to −0.028; significant heterogeneity: I2 = 83.962). Meta-regression identified age (p < 0.001) and MMSE scores (p < 0.001) to be the significant moderators that could explain the heterogeneity in findings in these studies. Additionally, there were no significant differences in serum BDNF levels between patients with AD and MCI (eight studies, n = 906) and between MCI and HC (nine studies, n = 5090). In all, patients with AD, but not MCI, have significantly lower serum BDNF levels compared to healthy controls. This meta-analysis confirmed the direction of change in serum BDNF levels in dementia. This finding suggests that a significant change in peripheral BDNF levels can only be detected at the late stage of the dementia spectrum. Molecular mechanisms, implications on interventional trials, and future directions for studies examining BDNF in dementia were discussed.

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.

scholarly journals SAT0081 FOOTPRINT OF THE BRAIN-DERIVED NEUROTROPHIC FACTOR ON PAIN AND MOOD PERCEPTION OF PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 975.3-975
Author(s):  
L. Leifsdottir ◽  
C. Wasen ◽  
M. C. Erlandsson ◽  
K. M. Andersson ◽  
R. Heckemann ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Neurotrophic Factor ◽  
Pain Threshold ◽  
Molecular Mechanisms ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
High Serum ◽  
Brain Volumes ◽  
Patient Reported ◽  
Serum Bdnf

Background:Depression and cognitive impairment have been frequently reported in rheumatoid arthritis (RA) (1). Studies of the molecular mechanisms behind these phenomena attract increasing attention. We previously reported that signaling through the insulin-like receptor is impaired in RA and has consequences for pain processing (2).Objectives:We investigated the central and peripheral footprint of the major neurotrophin in the central nervous system, brain-derived neurotrophic factor (BDNF), on pain and mood perception of RA patients.Methods:Pain symptomatology was assessed in 216 female RA patients (mean age 52y, mean disease duration 10 years) by a visual analogue scale (VAS), 18 tender points count (TPC), and by pressure-induced pain threshold measurement. The mood was patient-reported based on the Hospital Anxiety and Depression Scale (HADS). Clinical RA activity was assessed by DAS28. Serum levels of BDNF, IL6, IL1b, IL10 and IFN-gamma were measured by ELISA. Transcription of FOXO1 and FOXO3 was measured by RT-PCR in whole-blood RNA. Effect of BDNF signaling in leukocytes was assessed by differentially expressed gene (DEG) analysis in RNAseq of 24 female RA patients (R-studio, Bioconductor). High-resolution brain MRI was performed in a representative selection of 16 patients. Brain volumes were analyzed with MAPER software for accurate measurement of 83 anatomical regions (3) and compared between two groups of patients with high and low serum BDNF, respectively.Results:In RA patients, high serum levels of BDNF were associated with low TPC (4.1 vs 5.3, p=0.04) and higher pain threshold (kPa, 416 vs 382, p=0.09). No connection between BDNF and mood measures was evident. High BDNF was associated with high serum VEGF (p<0,001), IFNg (p=0.0004), IL1b (p=0.036) and serum insulin (p<0,001), but low resistin (p=0.059). No correlation was found between BDNF with either serum IGF1 or inflammation parameters DAS28 and IL6. Serum BDNF was functional, since the RA patients with high BDNF had significantly larger brain volumes in specific regions and significantly lower FOXO1 mRNA in blood leukocytes (p=0.03). Specifically, structures of the limbic system, parahippocampus, lingual gyrus, nucleus accumbens and thalamus, key regions for the transmission of nociceptive information and central modulation of pain, were enlarged. BDNF production was measured in CD4-CD8- PBMC and was inversely related to expression of its high-affinity receptor TrkB in CD4+ PBMC. DEG analysis in CD4 T cells showed that low TrkB was associated with CD28+ transitional memory phenotype.Conclusion:We conclude that high serum BDNF was associated with larger volumes of nociception-related brain regions and lower pain perception, acting independently of IGF1 and systemic inflammation.References:[1] Dougados M, Curr OppRheumatol 2016[2] Andersson, Wasen, PNAS2017[3] Heckemann, NeuroImage 2010Disclosure of Interests:None declared

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