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BDNF and Synaptic Plasticity, Cognitive Function, and Dysfunction

  • B. Lu
  • G. Nagappan
  • Y. Lu
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 220)

Abstract

Among all neurotrophins, brain-derived neurotrophic factor (BDNF) stands out for its high level of expression in the brain and its potent effects on synapses. It is now widely accepted that the main function of BDNF in the adult brain is to regulate synapses, with structural and functional effects ranging from short-term to long-lasting, on excitatory or inhibitory synapses, in many brain regions. The diverse effects of BDNF on brain synapses stem from its complex downstream signaling cascades, as well as the diametrically opposing effects of the pro- and mature form through distinct receptors, TrkB and p75NTR. Many aspects of BDNF cell biology are regulated by neuronal activity. The synergistic interactions between neuronal activity and synaptic plasticity by BDNF make it an ideal and essential regulator of cellular processes that underlie cognition and other complex behaviors. Indeed, numerous studies firmly established that BDNF plays a critical role in hippocampal long-term potentiation (LTP), a long-term enhancement of synaptic efficacy thought to underlie learning and memory. Converging evidence now strongly suggest that deficits in BDNF signaling contribute to the pathogenesis of several major diseases and disorders such as Huntington’s disease, Alzheimer’s disease, and depression. Thus, manipulating BDNF pathways represents a viable treatment approach to a variety of neurological and psychiatric disorders.

Keywords

Brain-derived neurotrophic factor Synaptic plasticity mRNA trafficking 

Abbreviations

BDNF

Brain-derived neurotrophic factor

BDNF-KIV

BDNF GFP knockin in exon IV

CA1/CA3

Cornu ammonis areas 1 and 3

E-LTP

Early phase long-term potentiation

GAD

Glutamate decarboxylase

HA

Hemagglutinin

HFS

High frequency stimulation

IgG

Immunoglobulin

KO

Knockout

L-LTP

Late phase long-term potentiation

LTD

Long-term depression

mBDNF

Mature BDNF

MMP

Matrix metalloprotease

MRI

Magnetic resonance imaging

NMDAR

N-methyl-d-aspartate receptor

p75NTR

p75 neurotrophin receptor

proBDNF

Precursor BDNF

PRP

Plasticity-related protein

PV

Parvalbumin

SNP

Single nucleotide polymorphism

STDP

Spike time-dependent plasticity

TBS

Theta burst stimulation

tDCS

Transcranial direct current stimulation

tPA

Tissue plasminogen activator

TrkB

Tropomyosin-related kinase B

UTR

Untranslated region

Val66Met

Valine 66 to methionine

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014 2014

Authors and Affiliations

  1. 1.GlaxoSmithKline, R&D ChinaPudong, ShanghaiChina
  2. 2.Department of Psychiatry, Roy J. and Lucille A. Carver College of MedicineThe University of IowaIowa CityUSA

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