Volume 586, Issue 23 p. 5717-5725
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A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS

Binith Cheeran

Binith Cheeran

Institute of Neurology, Queen Square, London WC1N 3BG, UK

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Penelope Talelli

Penelope Talelli

Institute of Neurology, Queen Square, London WC1N 3BG, UK

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Francesco Mori

Francesco Mori

Institute of Neurology, Queen Square, London WC1N 3BG, UK

Fondazione S. Lucia I.R.C.C.S and Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy

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Giacomo Koch

Giacomo Koch

Institute of Neurology, Queen Square, London WC1N 3BG, UK

Fondazione S. Lucia I.R.C.C.S and Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy

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Antonio Suppa

Antonio Suppa

Institute of Neurology, Queen Square, London WC1N 3BG, UK

Department of Neurological Sciences and Neuromed Institute, Sapienza University of Rome, Rome, Italy

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Mark Edwards

Mark Edwards

Institute of Neurology, Queen Square, London WC1N 3BG, UK

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Henry Houlden

Henry Houlden

Institute of Neurology, Queen Square, London WC1N 3BG, UK

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Kailash Bhatia

Kailash Bhatia

Institute of Neurology, Queen Square, London WC1N 3BG, UK

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Richard Greenwood

Richard Greenwood

Institute of Neurology, Queen Square, London WC1N 3BG, UK

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John C. Rothwell

John C. Rothwell

Institute of Neurology, Queen Square, London WC1N 3BG, UK

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First published: 28 November 2008
Citations: 529
Corresponding author B. Cheeran: Institute of Neurology, Queen Square, London WC1N 3BG, UK. Email: [email protected]

Abstract

The brain-derived neurotrophic factor gene (BDNF) is one of many genes thought to influence synaptic plasticity in the adult brain and shows a common single nucleotide polymorphism (BDNF Val66Met) in the normal population that is associated with differences in hippocampal volume and episodic memory. It is also thought to influence possible synaptic changes in motor cortex following a simple motor learning task. Here we extend these studies by using new non-invasive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) techniques that directly test the excitability and plasticity of neuronal circuits in human motor cortex in subjects at rest. We investigated whether the susceptibility to TMS probes of plasticity is significantly influenced by the BDNF polymorphism. Val66Met carriers were matched with Val66Val individuals and tested on the following protocols: continuous and intermittent theta burst TMS; median nerve paired associative stimulation; and homeostatic plasticity in the TDCS/1 Hz rTMS model. The response of Met allele carriers differed significantly in all protocols compared with the response of Val66Val individuals. We suggest that this is due to the effect of BNDF on the susceptibility of synapses to undergo LTP/LTD. The circuits tested here are implicated in the pathophysiology of movement disorders such as dystonia and are being assessed as potential new targets in the treatment of stroke. Thus the polymorphism may be one factor that influences the natural response of the brain to injury and disease.