June 4, 2009 Until now diseases like schizophrenia and bipolar disorder have been difficult to study biologically, since this would entail taking samples from the patient’s brain. But new research findings from Örebro University in Sweden show that it is just as good to study a certain type of skin cells, since they function in a way that is similar to a type of brain cells that are suspected of playing a major role in both disorders.
“Among other benefits, this makes it considerably easier to develop and test new drugs,” says Ravi Vumma, and the head of the research group Nikolaos Venizelos who is presenting the findings in the journal Neuroscience Letters.
One of the causes of schizophrenia and bipolar disorder (previously called manic-depressive syndrome) is assumed to be that the level of important transmitter substances in the brain is too low, which negatively impacts the transmission of signals. That, in turn, is because the cells in the blood-brain barrier are not transporting enough of the amino acids that are needed for the brain to be able to produce signal substances like dopamine, noradrenalin, and serotonin.
“Altered transport of the amino acids tyrosine and tryptophan may be one explanation for the disrupted signal transmission in patients with schizophrenia and bipolar disorder,” Ravi Vumma explains.
We have therefore mapped how the transport of the two amino acids takes place, what paths they take into the cell. Various amino acids use different transport systems, and to enhance our knowledge about schizophrenia and bipolar disorder it is necessary to identify which systems are relevant for tyrosine and tryptophan.
Moreover, we want to find out whether connective tissue cells in the skin, fibroblasts, transport amino acids in the same way as endothelial cells in the brain, as this would constitute a dramatic enhancement of our ability to study how substances pass through the blood-brain barrier. The two cell types have a similar membrane function, to close out undesirable substances and only transport substances the body needs.
“The research shows that tyrosine and tryptophan largely use the same transport system and that it functions in the same way in both skin fibroblasts and the endothelial cells of the blood-brain barrier.”
On top of this we were able to determine that the inward transport of tyrosine in fibroblasts was lower in patients with bipolar disorder compared with a healthy control group. Since previous research has shown that it was lower in individuals with schizophrenia, his discovery indicates that the two diseases involve a common alteration that is probably caused by a common genetic variation.
The head of the research group Nikolaos Venizelos says that Ravi Vumma’s discoveries show that human skin fibroblasts can be used for studying the transport of both amino acids and drugs that use the same transport system. One of the problems today is that only a few of the drugs being developed to affect the brain are able to get through the blood-brain barrier, which means that they cannot have the desired effect.
Journal reference: Neuroscience Letters Volume 457, Issue 1, 19 June 2009, Pages 49-5.
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