Abstract

Brain-derived neurotrophic factor (BDNF) is one of the most distributed and extensively studied neurotrophins in the mammalian brain. BDNF signals through the tropomycin receptor kinase B (TrkB) and the low affinity p75 neurotrophin receptor (p75NTR). BDNF plays an important role in proper growth, development, and plasticity of glutamatergic and GABAergic synapses and through modulation of neuronal differentiation, it influences serotonergic and dopaminergic neurotransmission. BDNF acts as paracrine and autocrine factor, on both pre-synaptic and post-synaptic target sites. It is crucial in the transformation of synaptic activity into long-term synaptic memories. BDNF is considered an instructive mediator of functional and structural plasticity in the central nervous system (CNS), influencing dendritic spines and, at least in the hippocampus, the adult neurogenesis. Changes in the rate of adult neurogenesis and in spine density can influence several forms of learning and memory and can contribute to depression-like behaviors. The possible roles of BDNF in neuronal plasticity highlighted in this review focus on the effect of antidepressant therapies on BDNF-mediated plasticity. Moreover, we will review data that illustrate the role of BDNF as a potent protective factor that is able to confer protection against neurodegeneration, in particular in Alzheimer’s disease. Finally, we will give evidence of how the involvement of BDNF in the pathogenesis of brain glioblastoma has emerged, thus opening new avenues for the treatment of this deadly cancer.

Highlights

  • The neurotrophin Brain-derived neurotrophic factor (BDNF) is one of the most studied and well characterized neurotrophic factors in the central nervous system (CNS)

  • Several lines of evidence suggest that the BDNF/tropomycin receptor kinase B (TrkB) signaling is involved in adult neurogenesis in the hippocampus with differing effects in the dentate gyrus (DG) and subventricular zone (SVZ) [5]

  • BDNF is one of the most inspiring molecules to better understand the disadvantageous synaptic learning underlying the etiology of depression, accompanied by declines in the rate of adult neurogenesis and in spine densities [181]

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Summary

Introduction

Several lines of evidence suggest that the BDNF/TrkB signaling is involved in adult neurogenesis in the hippocampus with differing effects in the dentate gyrus (DG) and subventricular zone (SVZ) [5]. BDNF protein is detectable outside of the nervous system in several non-neuronal tissues, such as in endothelial cells [17,18], cardiomyocytes [19], vascular smooth muscle cells [17], leukocytes [20], platelets [21,22], and megakaryocytes [19] It may be involved in cancer, angiogenesis, reduction of glucose production from the liver [23], and in the uptake of glucose in peripheral tissues (see [24] for review). We touch on the newly emerging role of BDNF in the pathogenesis of brain gliomas

BDNF Transcripts
Biology of BDNF
The Human BDNF Variant Val66Met
Major Depressive Disorder
BDNF and Neuronal Plasticity
BDNF and Synaptic Plasticity
BDNF in Depressed Patients
BDNF and Antidepressant Treatments
Beneficial Effects of Exercise on Plasticity
The Protective Role of BDNF on Neurodegeneration
The Protective Role of BDNF on Alzheimer’s Disease
BDNF and Ras-ERK-CREB Signaling in Alzheimer’s Disease
BDNF and Brain Cancer
Findings
Conclusions

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