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Brain-Derived Neurotrophic Factor 2018

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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 December 2018) | Viewed by 81834

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Special Issue Editors

Prof. Dr. Kenji Hashimoto

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Guest Editor

Division of Clinical Neuroscience, Center for Forensic Mental Health, Chiba University, Chiba, Japan
Interests: brain body axis; neuropsychiatric disorder; neurotrophic factors; neuroplasticity
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Guiting Lin

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Guest Editor

University of California, San Francisco
Interests: Dr. Guiting Lin has conducted research work exploring the effect of brain-derived neurotrophic factor (BDNF) on the regeneration of nitric oxide synthesis (NOS) penile nerves and the neurons in the pelvic ganglia after cavernous nerve transection in rats. The results showed that the BDNF significantly enhanced the regeneration of NOS-containing fibers in the dorsal and intracavernosal nerves. It was also found that BDNF promoted penile nerve regeneration through signal transducer and activator of transcription (STAT), mitogen-activated protein kinases (MAPKs) and protein kinase C (PKC) cellular signaling pathways in the ganglion. Meanwhile, Dr. Lin has applied the rat oligo microarray to screen differential genes related to incontinence in a rat model and the molecular mechanism of female stress urinary incontinence (SUI). Recently, Dr. Guiting Lin has focused on tissue resident stem/progenitor cells and the application of microenergy medicine (MEM) in urology, such as SUI and erectile dysfunction (ED). D
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

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
Assoc. Prof. Dr. Guiting Lin
Guest Editors

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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
Tropomyosin-related kinase B (TrkB)

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Research

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16 pages, 1681 KiB

Open AccessArticle

Increased Brain-Derived Neurotrophic Factor in Lumbar Dorsal Root Ganglia Contributes to the Enhanced Exercise Pressor Reflex in Heart Failure

by Alicia M. Schiller, Juan Hong, Zhiqiu Xia and Han-Jun Wang

Int. J. Mol. Sci. 2019, 20(6), 1480; https://doi.org/10.3390/ijms20061480 - 24 Mar 2019

Cited by 10 | Viewed by 3418

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 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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19 pages, 3280 KiB

Open AccessArticle

Disease Affects Bdnf Expression in Synaptic and Extrasynaptic Regions of Skeletal Muscle of Three SBMA Mouse Models

by Katherine Halievski, Samir R. Nath, Masahisa Katsuno, Hiroaki Adachi, Gen Sobue, S. Marc Breedlove, Andrew P. Lieberman and Cynthia L. Jordan

Int. J. Mol. Sci. 2019, 20(6), 1314; https://doi.org/10.3390/ijms20061314 - 15 Mar 2019

Cited by 5 | Viewed by 4108

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 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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25 pages, 28591 KiB

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

by Renata Lejkowska, Miłosz Piotr Kawa, Ewa Pius-Sadowska, Dorota Rogińska, Karolina Łuczkowska, Bogusław Machaliński and Anna Machalińska

Int. J. Mol. Sci. 2019, 20(3), 777; https://doi.org/10.3390/ijms20030777 - 12 Feb 2019

Cited by 19 | Viewed by 4004

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 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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9 pages, 5221 KiB

Open AccessCommunication

Brain-Derived Neurotrophic Factor Is Required for the Neuroprotective Effect of Mifepristone on Immature Purkinje Cells in Cerebellar Slice Culture

by Jennifer Rakotomamonjy and Abdel Mouman Ghoumari

Int. J. Mol. Sci. 2019, 20(2), 285; https://doi.org/10.3390/ijms20020285 - 12 Jan 2019

Cited by 6 | Viewed by 3314

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 death. However, interestingly, BDNF haploinsufficiency impairs neuronal survival induced by mifepristone and GABA_A-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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20 pages, 3479 KiB

Open AccessArticle

Brain-Derived Neurotrophin and TrkB in Head and Neck Squamous Cell Carcinoma

by József Dudás, Anna Riml, Raphaela Tuertscher, Christian Pritz, Teresa Bernadette Steinbichler, Volker Hans Schartinger, Susanne Sprung, Rudolf Glueckert, Anneliese Schrott-Fischer, Lejo Johnson Chacko and Herbert Riechelmann

Int. J. Mol. Sci. 2019, 20(2), 272; https://doi.org/10.3390/ijms20020272 - 11 Jan 2019

Cited by 7 | Viewed by 5096

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 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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23 pages, 8209 KiB

Open AccessArticle

Comparison between Polybutylcyanoacrylate Nanoparticles with Either Surface-Adsorbed or Encapsulated Brain-Derived Neurotrophic Factor on the Neural Differentiation of iPSCs

by Martin Hsiu-Chu Lin, Chiu-Yen Chung, Kuo-Tai Chen, Jih-Chao Yeh, Tsong-Hai Lee, Ming-Hsueh Lee, I-Neng Lee, Wei-Chao Huang and Jen-Tsung Yang

Int. J. Mol. Sci. 2019, 20(1), 182; https://doi.org/10.3390/ijms20010182 - 06 Jan 2019

Cited by 10 | Viewed by 4105

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 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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13 pages, 4807 KiB

Open AccessArticle

Sub-Chronic Stress Exacerbates the Pro-Thrombotic Phenotype in BDNF^Val/Met Mice: Gene-Environment Interaction in the Modulation of Arterial Thrombosis

by Leonardo Sandrini, Alessandro Ieraci, Patrizia Amadio, Fabrizio Veglia, Maurizio Popoli, Francis S. Lee, Elena Tremoli and Silvia Stella Barbieri

Int. J. Mol. Sci. 2018, 19(10), 3235; https://doi.org/10.3390/ijms19103235 - 19 Oct 2018

Cited by 15 | Viewed by 3322

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 (BDNF^Val/Met) mice, suggesting an important relationship in terms of gene-environment interaction (GxE). However, the interplay between stress and BDNF^Val/Met in relation to CVD is completely unknown. Here, we showed that BDNF^Val/Met mice display a greater propensity to arterial thrombosis than wild type BDNF^Val/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 BDNF^Val/Met mice had a greater number of large and reticulated platelets but comparable number and maturation profile of bone marrow megakaryocytes compared to BDNF^Val/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 BDNF^Val/Val and BDNF^Val/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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8 pages, 330 KiB

Open AccessCommunication

Relationship between Serum BDNF Levels and Depressive Mood in Subacute Stroke Patients: A Preliminary Study

by Won Hyuk Chang, Min A Shin, Ahee Lee, Heegoo Kim and Yun-Hee Kim

Int. J. Mol. Sci. 2018, 19(10), 3131; https://doi.org/10.3390/ijms19103131 - 12 Oct 2018

Cited by 10 | Viewed by 3067

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 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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12 pages, 697 KiB

Open AccessReview

Interactions of Glutamatergic Neurotransmission and Brain-Derived Neurotrophic Factor in the Regulation of Behaviors after Nicotine Administration

by Jieun Kim, Ju Hwan Yang, In Soo Ryu, Sumin Sohn, Sunghyun Kim and Eun Sang Choe

Int. J. Mol. Sci. 2019, 20(12), 2943; https://doi.org/10.3390/ijms20122943 - 16 Jun 2019

Cited by 13 | Viewed by 4543

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 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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16 pages, 1284 KiB

Open AccessReview

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

by Jessica L. Fletcher, Simon S. Murray and Junhua Xiao

Int. J. Mol. Sci. 2018, 19(12), 4131; https://doi.org/10.3390/ijms19124131 - 19 Dec 2018

Cited by 76 | Viewed by 13931

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 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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23 pages, 1038 KiB

Open AccessReview

Actions of Brain-Derived Neurotrophin Factor in the Neurogenesis and Neuronal Function, and Its Involvement in the Pathophysiology of Brain Diseases

by Tadahiro Numakawa, Haruki Odaka and Naoki Adachi

Int. J. Mol. Sci. 2018, 19(11), 3650; https://doi.org/10.3390/ijms19113650 - 19 Nov 2018

Cited by 196 | Viewed by 7761

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 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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18 pages, 2128 KiB

Open AccessReview

Inwardly Rectifying Potassium Channel Kir4.1 as a Novel Modulator of BDNF Expression in Astrocytes

by Yukihiro Ohno, Masato Kinboshi and Saki Shimizu

Int. J. Mol. Sci. 2018, 19(11), 3313; https://doi.org/10.3390/ijms19113313 - 24 Oct 2018

Cited by 51 | Viewed by 9435

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 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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16 pages, 1110 KiB

Open AccessReview

BDNF, Brain, and Regeneration: Insights from Zebrafish

by Carla Lucini, Livia D’Angelo, Pietro Cacialli, Antonio Palladino and Paolo De Girolamo

Int. J. Mol. Sci. 2018, 19(10), 3155; https://doi.org/10.3390/ijms19103155 - 13 Oct 2018

Cited by 58 | Viewed by 8566

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 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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15 pages, 1516 KiB

Open AccessReview

Association between Obesity and Circulating Brain-Derived Neurotrophic Factor (BDNF) Levels: Systematic Review of Literature and Meta-Analysis

by Leonardo Sandrini, Alessandro Di Minno, Patrizia Amadio, Alessandro Ieraci, Elena Tremoli and Silvia S. Barbieri

Int. J. Mol. Sci. 2018, 19(8), 2281; https://doi.org/10.3390/ijms19082281 - 03 Aug 2018

Cited by 77 | Viewed by 6392

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 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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