Brain Peptide Boosts Neuronal Response to Dopamine
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LONDON (Reuters Health) May 08 - A team of French scientists has discovered a new role for brain-derived neurotrophic factor (BDNF) in behavioral sensitization to dopamine.
Because dopamine dysfunction has been implicated in a wide variety of disorders, including schizophrenia, Parkinson's disease and drug addiction, "the implications of these findings may be extensive," according to an editorial accompanying the report on the new study, both published in the May 3rd issue of Nature.
Previous studies by Dr. Pierre Sokoloff, of INSERM U 109 in Paris, and a multicenter team previously demonstrated that dopamine neurons release an unknown factor that regulates the D3 dopamine receptor. In their new report, they show that this factor is, in fact, BDNF.
Specifically, Dr. Sokoloff and his team demonstrated that the expression of D3 receptors is downregulated in mice lacking BDNF. Infusing BDNF back into the deficient mice reinstated normal D3 expression, indicating that the factor is critical to normal D3 expression in both early development and adulthood, according to the investigators.
Moreover, they showed that BDNF induces long-term behavioral sensitization to dopamine in rats with a form of Parkinson's disease. By treating the rats with BDNF, the scientists were able to induce overexpression of D3 receptors in the striatum, which they say indicates that the factor may play a role in the sensitization to levodopa that occurs with repeated treatment.
Prior to these studies, BDNF was thought to be involved primarily in the proliferation, differentiation and survival of brain neurons.
"The significance of the study is not only does it establish a new role for BDNF, but it also shows a unique feature of dopamine D3 receptors, in that these receptors, but not dopamine receptors D1 and D2, are regulated by the neurotrophic factor," editorialist Dr. Francis J. White told Reuters Health.
Dr. White, of The Chicago Medical School, added that although the findings could have important implications for treating D3-associated disorders, including Parkinson's disease, much more must be learned about the factor, and D3 receptors, before any role in treatment can be determined.
Nature 2001;411:35-38,86-89. |
