BDNF boost

In the 3 May Nature Oliver Guillin and colleagues report that the expression of the dopamine D3 receptor is regulated by the brain-derived neurotrophic factor (BDNF), a protein once thought to be needed simply for the proliferation and survival of neurons (Nature 2001, 411:86-89).D3 receptors are expressed mainly in an area of the brain known as the shell of the nucleus accumbens. Neurons from the ventral tegmental area (VTA), which produce both dopamine and BDNF, connect to neurons of the nucle

By | May 3, 2001

In the 3 May Nature Oliver Guillin and colleagues report that the expression of the dopamine D3 receptor is regulated by the brain-derived neurotrophic factor (BDNF), a protein once thought to be needed simply for the proliferation and survival of neurons (Nature 2001, 411:86-89).

D3 receptors are expressed mainly in an area of the brain known as the shell of the nucleus accumbens. Neurons from the ventral tegmental area (VTA), which produce both dopamine and BDNF, connect to neurons of the nucleus accumbens. Guillin et al show that in gene-targeted mice lacking BDNF, or in a rat model of Parkinson's disease (in which the dopamine-releasing neurons of the VTA are damaged by infusion of 6-hydroxydopamine), D3 receptors are not expressed in the nucleus accumbens shell. Infusion of BDNF into the shell restored the expression of the D3 receptor.

In the rat model dopamine-releasing neurons on only one side of the brain are damaged and when these rats were injected with levodopa (the precursor of dopamine), the expression of both the D3 receptor and the BDNF receptor TrkB increased. The injection caused the animals to turn away from the side of damage (levodopa-induced rotations) and this correlated with a higher activation of D3 receptors on the side of the damage. With repeated injections, this behaviour became more pronounced. The behavioural sensitisation and associated upregulation of D3 receptors was reduced when a BDNF antagonist was infused into the brain.

This suggests that BDNF is responsible for behavioural sensitisation to levodopa and might explain the abnormal movements seen in Parkinson's patients on long-term treatment with levodopa.

Guillin et al conclude that the regulation of D3 receptors by BDNF could be involved in a number of brain disorders involving abnormal D3 receptor expression including Parkinson's disease, schizophrenia and drug addiction.

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