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Special Issue "Brain-Derived Neurotrophic Factor 2020"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 October 2020).

Special Issue Editors

Dr. Abbas F. Sadikot
E-Mail Website
Guest Editor
Montreal Neurological Institute, McGill University, Montreal, QC, Canada
Prof. Dr. Guiting Lin
E-Mail Website
Guest Editor
Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, USA
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue “Brain-Derived Neurotrophic Factor 2018”. (https://www.mdpi.com/journal/ijms/special_issues/bdnf_2018)

This Special Issue, “Brain-Derived Neurotrophic Factor”, will cover a selection of recent research topics and current review articles in the field of mechanism, expression, function and neuroprotective effects of Brain-Derived Neurotrophic Factor in the central nerve and peripheral nerve system. Experimental papers, up-to-date review articles, and commentaries are all welcome.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. It acts on certain neurons of the central nervous system and the peripheral nervous system, helping to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses. BDNF plays a significant role in neuroprotective effects. BDNF can promote protective pathways and inhibit damaging pathways that contribute to the brain’s neurogenic response by enhancing cell survival. This becomes especially evident following suppression of tropomyosin-related kinase B (TrkB) activity. BDNF recently was found to enhance survival and neuronal differentiation of human neural precursor cells in rat models of auditory neuronal damage. BDNF from bone marrow-derived cells promoted post-injury repair of sciatic nerve in mice. Therefore, BDNF would represent an attractive treatment modality for nerve injuries in addition to peripheral neuropathic disorders, such as diabetes mellitus.

Prof. Dr. Kenji Hashimoto
Dr. Abbas F. Sadikot
Prof. Dr. Guiting Lin
Guest Editors

Manuscript Submission Information

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Keywords

  • Brain-Derived Neurotrophic Factor (BDNF)
  • Neuroprotection
  • Nerve regeneration
  • Survival and neuronal differentiation
  • Central nerve system
  • Peripheral nerve system
  • Cellular signaling transduction
  • Tropomyosin-related kinase B (TrkB)
  • Clinical trials

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Published Papers (18 papers)

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Research

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Open AccessArticle
BDNF Expression in Cortical GABAergic Interneurons
Int. J. Mol. Sci. 2020, 21(5), 1567; https://doi.org/10.3390/ijms21051567 - 25 Feb 2020
Cited by 3 | Viewed by 1137
Abstract
Brain-derived neurotrophic factor (BDNF) is a major neuronal growth factor that is widely expressed in the central nervous system. It is synthesized as a glycosylated precursor protein, (pro)BDNF and post-translationally converted to the mature form, (m)BDNF. BDNF is known to be produced and [...] Read more.
Brain-derived neurotrophic factor (BDNF) is a major neuronal growth factor that is widely expressed in the central nervous system. It is synthesized as a glycosylated precursor protein, (pro)BDNF and post-translationally converted to the mature form, (m)BDNF. BDNF is known to be produced and secreted by cortical glutamatergic principal cells (PCs); however, it remains a question whether it can also be synthesized by other neuron types, in particular, GABAergic interneurons (INs). Therefore, we utilized immunocytochemical labeling and reverse transcription quantitative PCR (RT-qPCR) to investigate the cellular distribution of proBDNF and its RNA in glutamatergic and GABAergic neurons of the mouse cortex. Immunofluorescence labeling revealed that mBDNF, as well as proBDNF, localized to both the neuronal populations in the hippocampus. The precursor proBDNF protein showed a perinuclear distribution pattern, overlapping with the rough endoplasmic reticulum (ER), the site of protein synthesis. RT-qPCR of samples obtained using laser capture microdissection (LCM) or fluorescence-activated cell sorting (FACS) of hippocampal and cortical neurons further demonstrated the abundance of BDNF transcripts in both glutamatergic and GABAergic cells. Thus, our data provide compelling evidence that BDNF can be synthesized by both principal cells and INs of the cortex. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2020)
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Open AccessArticle
Increased Brain-Derived Neurotrophic Factor in Lumbar Dorsal Root Ganglia Contributes to the Enhanced Exercise Pressor Reflex in Heart Failure
Int. J. Mol. Sci. 2019, 20(6), 1480; https://doi.org/10.3390/ijms20061480 - 24 Mar 2019
Cited by 5 | Viewed by 1239
Abstract
An exaggerated exercise pressor reflex (EPR) is associated with excessive sympatho-excitation and exercise intolerance in the chronic heart failure (CHF) state. We hypothesized that brain-derived neurotrophic factor (BDNF) causes the exaggerated EPR via sensitizing muscle mechanosensitive afferents in CHF. Increased BDNF expression was [...] Read more.
An exaggerated exercise pressor reflex (EPR) is associated with excessive sympatho-excitation and exercise intolerance in the chronic heart failure (CHF) state. We hypothesized that brain-derived neurotrophic factor (BDNF) causes the exaggerated EPR via sensitizing muscle mechanosensitive afferents in CHF. Increased BDNF expression was observed in lumbar dorsal root ganglia (DRGs) from CHF rats compared to sham rats. Immunofluorescence data showed a greater increase in the number of BDNF-positive neurons in medium and large-sized DRG subpopulations from CHF rats. Patch clamp data showed that incubation with BDNF for 4–6 h, significantly decreased the current threshold-inducing action potential (AP), threshold potential and the number of APs during current injection in Dil-labeled isolectin B4 (IB4)-negative medium-sized DRG neurons (mainly mechano-sensitive) from sham rats. Compared to sham rats, CHF rats exhibited an increased number of APs during current injection in the same DRG subpopulation, which was significantly attenuated by 4-h incubation with anti-BDNF. Finally, chronic epidural delivery of anti-BDNF attenuated the exaggerated pressor response to either static contraction or passive stretch in CHF rats whereas this intervention had no effect on the pressor response to hindlimb arterial injection of capsaicin. These data suggest that increased BDNF in lumbar DRGs contributes to the exaggerated EPR in CHF. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Open AccessArticle
Disease Affects Bdnf Expression in Synaptic and Extrasynaptic Regions of Skeletal Muscle of Three SBMA Mouse Models
Int. J. Mol. Sci. 2019, 20(6), 1314; https://doi.org/10.3390/ijms20061314 - 15 Mar 2019
Cited by 4 | Viewed by 1557
Abstract
Spinal bulbar muscular atrophy (SBMA) is a slowly progressive, androgen-dependent neuromuscular disease in men that is characterized by both muscle and synaptic dysfunction. Because gene expression in muscle is heterogeneous, with synaptic myonuclei expressing genes that regulate synaptic function and extrasynaptic myonuclei expressing [...] Read more.
Spinal bulbar muscular atrophy (SBMA) is a slowly progressive, androgen-dependent neuromuscular disease in men that is characterized by both muscle and synaptic dysfunction. Because gene expression in muscle is heterogeneous, with synaptic myonuclei expressing genes that regulate synaptic function and extrasynaptic myonuclei expressing genes to regulate contractile function, we used quantitative PCR to compare gene expression in these two domains of muscle from three different mouse models of SBMA: the “97Q” model that ubiquitously expresses mutant human androgen receptor (AR), the 113Q knock-in (KI) model that expresses humanized mouse AR with an expanded glutamine tract, and the “myogenic” model that overexpresses wild-type rat AR only in skeletal muscle. We were particularly interested in neurotrophic factors because of their role in maintaining neuromuscular function via effects on both muscle and synaptic function, and their implicated role in SBMA. We confirmed previous reports of the enriched expression of select genes (e.g., the acetylcholine receptor) in the synaptic region of muscle, and are the first to report the synaptic enrichment of others (e.g., glial cell line-derived neurotrophic factor). Interestingly, all three models displayed comparably dysregulated expression of most genes examined in both the synaptic and extrasynaptic domains of muscle, with only modest differences between regions and models. These findings of comprehensive gene dysregulation in muscle support the emerging view that skeletal muscle may be a prime therapeutic target for restoring function of both muscles and motoneurons in SBMA. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Open AccessArticle
Preclinical Evaluation of Long-Term Neuroprotective Effects of BDNF-Engineered Mesenchymal Stromal Cells as Intravitreal Therapy for Chronic Retinal Degeneration in Rd6 Mutant Mice
Int. J. Mol. Sci. 2019, 20(3), 777; https://doi.org/10.3390/ijms20030777 - 12 Feb 2019
Cited by 8 | Viewed by 1424
Abstract
This study aimed to investigate whether the transplantation of genetically engineered bone marrow-derived mesenchymal stromal cells (MSCs) to overexpress brain-derived neurotrophic factor (BDNF) could rescue the chronic degenerative process of slow retinal degeneration in the rd6 (retinal degeneration 6) mouse model and sought [...] Read more.
This study aimed to investigate whether the transplantation of genetically engineered bone marrow-derived mesenchymal stromal cells (MSCs) to overexpress brain-derived neurotrophic factor (BDNF) could rescue the chronic degenerative process of slow retinal degeneration in the rd6 (retinal degeneration 6) mouse model and sought to identify the potential underlying mechanisms. Rd6 mice were subjected to the intravitreal injection of lentivirally modified MSC-BDNF or unmodified MSC or saline. In vivo morphology, electrophysiological retinal function (ERG), and the expression of apoptosis-related genes, as well as BDNF and its receptor (TrkB), were assessed in retinas collected at 28 days and three months after transplantation. We observed that cells survived for at least three months after transplantation. MSC-BDNF preferentially integrated into the outer retinal layers and considerably rescued damaged retinal cells, as evaluated by ERG and immunofluorescence staining. Additionally, compared with controls, the therapy with MSC-BDNF was associated with the induction of molecular changes related to anti-apoptotic signaling. In conclusion, BDNF overexpression observed in retinas after MSC-BDNF treatment could enhance the neuroprotective properties of transplanted autologous MSCs alone in the chronically degenerated retina. This research provides evidence for the long-term efficacy of genetically-modified MSC and may represent a strategy for treating various forms of degenerative retinopathies in the future. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Open AccessCommunication
Brain-Derived Neurotrophic Factor Is Required for the Neuroprotective Effect of Mifepristone on Immature Purkinje Cells in Cerebellar Slice Culture
Int. J. Mol. Sci. 2019, 20(2), 285; https://doi.org/10.3390/ijms20020285 - 12 Jan 2019
Cited by 3 | Viewed by 1410
Abstract
Endogenous γ-aminobutyric acid (GABA)-dependent activity induces death of developing Purkinje neurons in mouse organotypic cerebellar cultures and the synthetic steroid mifepristone blocks this effect. Here, using brain-derived neurotrophic factor (BDNF) heterozygous mice, we show that BDNF plays no role in immature Purkinje cell [...] Read more.
Endogenous γ-aminobutyric acid (GABA)-dependent activity induces death of developing Purkinje neurons in mouse organotypic cerebellar cultures and the synthetic steroid mifepristone blocks this effect. Here, using brain-derived neurotrophic factor (BDNF) heterozygous mice, we show that BDNF plays no role in immature Purkinje cell death. However, interestingly, BDNF haploinsufficiency impairs neuronal survival induced by mifepristone and GABAA-receptors antagonist (bicuculline) treatments, indicating that the underlying neuroprotective mechanism requires the neurotrophin full expression. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Open AccessArticle
Brain-Derived Neurotrophin and TrkB in Head and Neck Squamous Cell Carcinoma
Int. J. Mol. Sci. 2019, 20(2), 272; https://doi.org/10.3390/ijms20020272 - 11 Jan 2019
Cited by 3 | Viewed by 2019
Abstract
We hypothesized that in head and neck squamous cell carcinoma (HNSCC), the neurotrophin brain-derived neurotrophic factor (BDNF) and its high affinity receptor TrkB regulate tumor cell survival, invasion, and therapy resistance. We used in situ hybridization for BDNF and immunohistochemistry (IHC) for TrkB [...] Read more.
We hypothesized that in head and neck squamous cell carcinoma (HNSCC), the neurotrophin brain-derived neurotrophic factor (BDNF) and its high affinity receptor TrkB regulate tumor cell survival, invasion, and therapy resistance. We used in situ hybridization for BDNF and immunohistochemistry (IHC) for TrkB in 131 HNSCC samples. Brain-derived neurotrophic factor was highly expressed in normal mucosa in HNSCC tissue and in cell lines, whereas only 42.74% of HNSCC tissue was TrkB+. One fourth of HNSCC cases was human papilloma virus (HPV) positive, but the TrkB IHC frequency was not different in HPV-positive (HPV+) and negative cases. The UPCI-SCC090 cells expressed constitutive levels of TrkB. Transforming-growth-factor-β1 (1 ng/mL TGF-β1) induced TrkB in a subpopulation of SCC-25 cells. A single 10-µg/mL mitomycin C treatment in UPCI-SCC090 cells induced apoptosis and BDNF did not rescue them. The SCC-25 cells were resistant to the MMC treatment, and their growth decreased after TGF-β1 treatment, but was restored by BDNF if it followed TGF-β1. Taken together, BDNF might be ineffective in HPV+ HNSCC patients. In HPV HNSCC patients, tumor cells did not die after chemotherapeutic challenge and BDNF with TGF-β1 could improve tumor cell survival and contribute to worse patient prognosis. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Open AccessArticle
Comparison between Polybutylcyanoacrylate Nanoparticles with Either Surface-Adsorbed or Encapsulated Brain-Derived Neurotrophic Factor on the Neural Differentiation of iPSCs
Int. J. Mol. Sci. 2019, 20(1), 182; https://doi.org/10.3390/ijms20010182 - 06 Jan 2019
Cited by 4 | Viewed by 1657
Abstract
The brain-derived neurotrophic factor (BDNF) is vital in the neural differentiation of neural stem/progenitor cells, and together may have therapeutic potential for neural regeneration. In this study, a multiplexed polybutylcyanoacrylate nanoparticle (PBCA NP) delivery platform was constructed, incorporating either surface-adsorbed or encapsulated BDNF [...] Read more.
The brain-derived neurotrophic factor (BDNF) is vital in the neural differentiation of neural stem/progenitor cells, and together may have therapeutic potential for neural regeneration. In this study, a multiplexed polybutylcyanoacrylate nanoparticle (PBCA NP) delivery platform was constructed, incorporating either surface-adsorbed or encapsulated BDNF for the induction of neural differentiation in induced pleuripotent stem cells (iPSCs), where tween 80 (T80) and superparamagnetic iron oxide (SPIO) were added for central nervous system (CNS) targeting and magnetic resonance (MR) image tracking, respectively. Both methods by which the BDNF was carried resulted in loading efficiencies greater than 95%. The nanoparticle-mediated delivery of BDNF resulted in neural differentiation of iPSCs detected on immunofluorescence staining as early as 7 days, with enhanced differentiation efficiency by 1.3-fold compared to the control on flow cytometry; the delivery system of surface-adsorbed BDNF gave rise to cells that had the best neural development than the encapsulated formulation. T80-coating disrupted the in vitro blood–brain barrier model with a corresponding 1.5- to two-fold increase in permeability. SPIO-loaded PBCA NPs exhibited a concentration-dependent, rapid decay in signal intensity on the phantom MR experiment. This study demonstrates the versatility of the PBCA NP, and the surface-adsorption of BDNF is the preferred method of delivery for the differentiation of iPSCs. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Open AccessArticle
Sub-Chronic Stress Exacerbates the Pro-Thrombotic Phenotype in BDNFVal/Met Mice: Gene-Environment Interaction in the Modulation of Arterial Thrombosis
Int. J. Mol. Sci. 2018, 19(10), 3235; https://doi.org/10.3390/ijms19103235 - 19 Oct 2018
Cited by 7 | Viewed by 1355
Abstract
Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism has been associated with increased susceptibility to develop mood disorders and recently it has been also linked with cardiovascular disease (CVD). Interestingly, stressful conditions unveil the anxious/depressive-like behavioral phenotype in heterozygous BDNFVal66Met (BDNFVal/Met) mice, suggesting [...] Read more.
Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism has been associated with increased susceptibility to develop mood disorders and recently it has been also linked with cardiovascular disease (CVD). Interestingly, stressful conditions unveil the anxious/depressive-like behavioral phenotype in heterozygous BDNFVal66Met (BDNFVal/Met) mice, suggesting an important relationship in terms of gene-environment interaction (GxE). However, the interplay between stress and BDNFVal/Met in relation to CVD is completely unknown. Here, we showed that BDNFVal/Met mice display a greater propensity to arterial thrombosis than wild type BDNFVal/Val mice after 7 days of restraint stress (RS). RS markedly increased the number of leukocytes and platelets, and induced hyper-responsive platelets as showed by increased circulating platelet/leukocyte aggregates and enhanced expression of P-selectin and GPIIbIIIa in heterozygous mutant mice. In addition, stressed BDNFVal/Met mice had a greater number of large and reticulated platelets but comparable number and maturation profile of bone marrow megakaryocytes compared to BDNFVal/Val mice. Interestingly, RS led to a significant reduction of BDNF expression accompanied by an increased activity of tissue factor in the aorta of both BDNFVal/Val and BDNFVal/Met mice. In conclusion, we provide evidence that sub-chronic stress unveils prothrombotic phenotype in heterozygous BDNF Val66Met mice affecting both the number and functionality of blood circulating cells, and the expression of key thrombotic molecules in aorta. Human studies will be crucial to understand whether this GxE interaction need to be taken into account in risk stratification of coronary artery disease (CAD) patients. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Open AccessCommunication
Relationship between Serum BDNF Levels and Depressive Mood in Subacute Stroke Patients: A Preliminary Study
Int. J. Mol. Sci. 2018, 19(10), 3131; https://doi.org/10.3390/ijms19103131 - 12 Oct 2018
Cited by 5 | Viewed by 1318
Abstract
The aim of this preliminary study was to investigate the potential of serum brain-derived neurotrophic factor (BDNF) as a biomarker in poststroke depressive mood in subacute stroke patients. Thirty-eight subacute stroke patients were recruited in this study. All participants underwent the standard rehabilitation [...] Read more.
The aim of this preliminary study was to investigate the potential of serum brain-derived neurotrophic factor (BDNF) as a biomarker in poststroke depressive mood in subacute stroke patients. Thirty-eight subacute stroke patients were recruited in this study. All participants underwent the standard rehabilitation program that included 2 h of physical therapy daily and 1 h of occupational therapy five days a week. The rehabilitation period lasted two weeks during the subacute stroke phase. We measured the serum BDNF, proBDNF, and matrix metalloproteinase-9 before and one and two weeks after the standard rehabilitation program. In addition, all participants were assessed using the Geriatric Depression Scale-Short Form (GDS-SF) for depressive mood at three time points. Pearson correlation analysis was performed to determine the relationship between serum BDNF levels and the GDS-SF. The GDS-SF showed significant improvement during the standard rehabilitation program period (p < 0.05). The GDS-SF was significantly correlated with serum BDNF levels at each time point (p < 0.05). These results suggest that serum BDNF may be used as a biomarker for depressive mood in subacute stroke patients. However, further studies with larger study populations are needed to clarify these results. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Review

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Open AccessReview
The Relationships Between Stress, Mental Disorders, and Epigenetic Regulation of BDNF
Int. J. Mol. Sci. 2020, 21(4), 1375; https://doi.org/10.3390/ijms21041375 - 18 Feb 2020
Cited by 2 | Viewed by 1061
Abstract
Brain-derived neurotrophic factor (BDNF), a critical member of the neurotrophic family, plays an important role in multiple stress-related mental disorders. Although alterations in BDNF in multiple brain regions of individuals experiencing stress have been demonstrated in previous studies, it appears that a set [...] Read more.
Brain-derived neurotrophic factor (BDNF), a critical member of the neurotrophic family, plays an important role in multiple stress-related mental disorders. Although alterations in BDNF in multiple brain regions of individuals experiencing stress have been demonstrated in previous studies, it appears that a set of elements are involved in the complex regulation. In this review, we summarize the specific brain regions with altered BDNF expression during stress exposure. How various environmental factors, including both physical and psychological stress, affect the expression of BDNF in specific brain regions are further summarized. Moreover, epigenetic regulation of BDNF, including DNA methylation, histone modification, and noncoding RNA, in response to diverse types of stress, as well as sex differences in the sensitivity of BDNF to the stress response, is also summarized. Clarification of the underlying role of BDNF in the stress process will promote our understanding of the pathology of stress-linked mental disorders and provide a potent target for the future treatment of stress-related illness. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2020)
Open AccessReview
BDNF as a Promising Therapeutic Agent in Parkinson’s Disease
Int. J. Mol. Sci. 2020, 21(3), 1170; https://doi.org/10.3390/ijms21031170 - 10 Feb 2020
Cited by 29 | Viewed by 2532
Abstract
Brain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. In animal models of Parkinson’s disease (PD), BDNF enhances the survival of dopaminergic neurons, improves dopaminergic neurotransmission and motor performance. Pharmacological therapies of PD are symptom-targeting, and their effectiveness decreases with the progression of the [...] Read more.
Brain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. In animal models of Parkinson’s disease (PD), BDNF enhances the survival of dopaminergic neurons, improves dopaminergic neurotransmission and motor performance. Pharmacological therapies of PD are symptom-targeting, and their effectiveness decreases with the progression of the disease; therefore, new therapeutical approaches are needed. Since, in both PD patients and animal PD models, decreased level of BDNF was found in the nigrostriatal pathway, it has been hypothesized that BDNF may serve as a therapeutic agent. Direct delivery of exogenous BDNF into the patient’s brain did not relieve the symptoms of disease, nor did attempts to enhance BDNF expression with gene therapy. Physical training was neuroprotective in animal models of PD. This effect is mediated, at least partly, by BDNF. Animal studies revealed that physical activity increases BDNF and tropomyosin receptor kinase B (TrkB) expression, leading to inhibition of neurodegeneration through induction of transcription factors and expression of genes related to neuronal proliferation, survival, and inflammatory response. This review focuses on the evidence that increasing BDNF level due to gene modulation or physical exercise has a neuroprotective effect and could be considered as adjunctive therapy in PD. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2020)
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Open AccessReview
Brain-Derived Neurotrophic Factor and Diabetes
Int. J. Mol. Sci. 2020, 21(3), 841; https://doi.org/10.3390/ijms21030841 - 28 Jan 2020
Cited by 4 | Viewed by 942
Abstract
Diabetes and its chronic complications still represent a great clinical problem, despite improvements made in the diagnosis and treatment of the disease. People with diabetes have a much higher risk of impaired brain function and psychiatric disorders. Neurotrophins are factors that protect neuronal [...] Read more.
Diabetes and its chronic complications still represent a great clinical problem, despite improvements made in the diagnosis and treatment of the disease. People with diabetes have a much higher risk of impaired brain function and psychiatric disorders. Neurotrophins are factors that protect neuronal tissue and improve the function of the central nervous system, and among them is brain-derived neurotrophic factor (BDNF). The level and function of BDNF in diabetes seems to be disturbed by and connected with the presence of insulin resistance. On the other hand, there is evidence for the highly beneficial impact of physical activity on brain function and BDNF level. However, it is not clear if this protective phenomenon works in the presence of diabetes. In this review, we summarize the current available research on this topic and find that the results of published studies are ambiguous. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2020)
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Open AccessReview
Interactions of Glutamatergic Neurotransmission and Brain-Derived Neurotrophic Factor in the Regulation of Behaviors after Nicotine Administration
Int. J. Mol. Sci. 2019, 20(12), 2943; https://doi.org/10.3390/ijms20122943 - 16 Jun 2019
Cited by 5 | Viewed by 1392
Abstract
Nicotine causes tobacco dependence, which may result in fatal respiratory diseases. The striatum is a key structure of forebrain basal nuclei associated with nicotine dependence. In the striatum, glutamate release is increased when α7 nicotinic acetylcholine receptors expressed in the glutamatergic terminals are [...] Read more.
Nicotine causes tobacco dependence, which may result in fatal respiratory diseases. The striatum is a key structure of forebrain basal nuclei associated with nicotine dependence. In the striatum, glutamate release is increased when α7 nicotinic acetylcholine receptors expressed in the glutamatergic terminals are exposed to nicotine, and over-stimulates glutamate receptors in gamma amino-butyric acid (GABA)ergic neurons. These receptor over-stimulations in turn potentiate GABAergic outputs to forebrain basal nuclei and contribute to the increase in psychomotor behaviors associated with nicotine dependence. In parallel with glutamate increases, nicotine exposure elevates brain-derived neurotrophic factor (BDNF) release through anterograde and retrograde targeting of the synapses of glutamatergic terminals and GABAergic neurons. This article reviews nicotine-exposure induced elevations of glutamatergic neurotransmission, the bidirectional targeting of BDNF in the striatum, and the potential regulatory role played by BDNF in behavioral responses to nicotine exposure. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Open AccessReview
Brain-Derived Neurotrophic Factor in Central Nervous System Myelination: A New Mechanism to Promote Myelin Plasticity and Repair
Int. J. Mol. Sci. 2018, 19(12), 4131; https://doi.org/10.3390/ijms19124131 - 19 Dec 2018
Cited by 22 | Viewed by 4137
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Open AccessReview
Actions of Brain-Derived Neurotrophin Factor in the Neurogenesis and Neuronal Function, and Its Involvement in the Pathophysiology of Brain Diseases
Int. J. Mol. Sci. 2018, 19(11), 3650; https://doi.org/10.3390/ijms19113650 - 19 Nov 2018
Cited by 70 | Viewed by 2284
Abstract
It is well known that brain-derived neurotrophic factor, BDNF, has an important role in a variety of neuronal aspects, such as differentiation, maturation, and synaptic function in the central nervous system (CNS). BDNF stimulates mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), phosphoinositide-3kinase (PI3K), and [...] Read more.
It is well known that brain-derived neurotrophic factor, BDNF, has an important role in a variety of neuronal aspects, such as differentiation, maturation, and synaptic function in the central nervous system (CNS). BDNF stimulates mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), phosphoinositide-3kinase (PI3K), and phospholipase C (PLC)-gamma pathways via activation of tropomyosin receptor kinase B (TrkB), a high affinity receptor for BDNF. Evidence has shown significant contributions of these signaling pathways in neurogenesis and synaptic plasticity in in vivo and in vitro experiments. Importantly, it has been demonstrated that dysfunction of the BDNF/TrkB system is involved in the onset of brain diseases, including neurodegenerative and psychiatric disorders. In this review, we discuss actions of BDNF and related signaling molecules on CNS neurons, and their contributions to the pathophysiology of brain diseases. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Open AccessReview
Inwardly Rectifying Potassium Channel Kir4.1 as a Novel Modulator of BDNF Expression in Astrocytes
Int. J. Mol. Sci. 2018, 19(11), 3313; https://doi.org/10.3390/ijms19113313 - 24 Oct 2018
Cited by 14 | Viewed by 2936
Abstract
Brain-derived neurotrophic factor (BDNF) is a key molecule essential for neural plasticity and development, and is implicated in the pathophysiology of various central nervous system (CNS) disorders. It is now documented that BDNF is synthesized not only in neurons, but also in astrocytes [...] Read more.
Brain-derived neurotrophic factor (BDNF) is a key molecule essential for neural plasticity and development, and is implicated in the pathophysiology of various central nervous system (CNS) disorders. It is now documented that BDNF is synthesized not only in neurons, but also in astrocytes which actively regulate neuronal activities by forming tripartite synapses. Inwardly rectifying potassium (Kir) channel subunit Kir4.1, which is specifically expressed in astrocytes, constructs Kir4.1 and Kir4.1/5.1 channels, and mediates the spatial potassium (K+) buffering action of astrocytes. Recent evidence illustrates that Kir4.1 channels play important roles in bringing about the actions of antidepressant drugs and modulating BDNF expression in astrocytes. Although the precise mechanisms remain to be clarified, it seems likely that inhibition (down-regulation or blockade) of astrocytic Kir4.1 channels attenuates K+ buffering, increases neuronal excitability by elevating extracellular K+ and glutamate, and facilitates BDNF expression. Conversely, activation (up-regulation or opening) of Kir4.1 channels reduces neuronal excitability by lowering extracellular K+ and glutamate, and attenuates BDNF expression. Particularly, the former pathophysiological alterations seem to be important in epileptogenesis and pain sensitization, and the latter in the pathogenesis of depressive disorders. In this article, we review the functions of Kir4.1 channels, with a focus on their regulation of spatial K+ buffering and BDNF expression in astrocytes, and discuss the role of the astrocytic Kir4.1-BDNF system in modulating CNS disorders. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Open AccessReview
BDNF, Brain, and Regeneration: Insights from Zebrafish
Int. J. Mol. Sci. 2018, 19(10), 3155; https://doi.org/10.3390/ijms19103155 - 13 Oct 2018
Cited by 18 | Viewed by 3034
Abstract
Zebrafish (Danio rerio) is a teleost fish widely accepted as a model organism for neuroscientific studies. The adults show common basic vertebrate brain structures, together with similar key neuroanatomical and neurochemical pathways of relevance to human diseases. However, the brain of [...] Read more.
Zebrafish (Danio rerio) is a teleost fish widely accepted as a model organism for neuroscientific studies. The adults show common basic vertebrate brain structures, together with similar key neuroanatomical and neurochemical pathways of relevance to human diseases. However, the brain of adult zebrafish possesses, differently from mammals, intense neurogenic activity, which can be correlated with high regenerative properties. Brain derived neurotrophic factor (BDNF), a member of the neurotrophin family, has multiple roles in the brain, due also to the existence of several biologically active isoforms, that interact with different types of receptors. BDNF is well conserved in the vertebrate evolution, with the primary amino acid sequences of zebrafish and human BDNF being 91% identical. Here, we review the available literature regarding BDNF in the vertebrate brain and the potential involvement of BDNF in telencephalic regeneration after injury, with particular emphasis to the zebrafish. Finally, we highlight the potential of the zebrafish brain as a valuable model to add new insights on future BDNF studies. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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Open AccessReview
Association between Obesity and Circulating Brain-Derived Neurotrophic Factor (BDNF) Levels: Systematic Review of Literature and Meta-Analysis
Int. J. Mol. Sci. 2018, 19(8), 2281; https://doi.org/10.3390/ijms19082281 - 03 Aug 2018
Cited by 21 | Viewed by 2021
Abstract
Reduction in brain-derived neurotrophic factor (BDNF) expression in the brain as well as mutations in BDNF gene and/or of its receptor are associated to obesity in both human and animal models. However, the association between circulating levels of BDNF and obesity is still [...] Read more.
Reduction in brain-derived neurotrophic factor (BDNF) expression in the brain as well as mutations in BDNF gene and/or of its receptor are associated to obesity in both human and animal models. However, the association between circulating levels of BDNF and obesity is still not defined. To answer this question, we performed a meta-analysis carrying out a systematic search in electronic databases. Ten studies (307 obese patients and 236 controls) were included in the analysis. Our data show that obese patients have levels of BDNF similar to those of controls (SMD: 0.01, 95% CI: −0.28, 0.30, p = 0.94). The lack of difference was further confirmed both in studies in which BDNF levels were assessed in serum (MD: −0.93 ng/mL, 95% CI: −3.34, 1.48, p = 0.45) and in plasma (MD: 0.15 ng/mL, 95% CI: −0.09, 0.39, p = 0.23). Data evaluation has shown that some bias might affect BDNF measurements (e.g., subject recruitment, procedures of sampling, handling, and storage), leading to a difficult interpretation of the results. Standardization of the procedures is still needed to reach strong, affordable, and reliable conclusions. Full article
(This article belongs to the Special Issue Brain-Derived Neurotrophic Factor 2018)
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