A lot can be too much – Hanna Lindgren defends her doctoral thesis

2009-03-19

So, even though we need dopamine, too much isn't good either?
– Yes, or rather, big fluctuations between high and low levels isn't good. When the peak levels of dopamine were cut off, the symptoms also decreased in our rat model, says Hanna Lindgren.

In Parkinson's Disease, muscle rigor and slow movements are among the principal motor symptoms. In patients with the disease, some of the brain cells that produce the transmitter substance dopamine die. The lack of dopamine causes problems for the patient to control movements.

The primary treatment for Parkinson patients is the administration of dopamine precursor L-dopa. This treatment usually works well to begin with, but after a couple of years the positive effects decrease and side effects, such as involuntary movements, dyskinesia, increase.

It is currently unknown why some patients easier develop dyskinesia, and there is no good treatment. Hanna Lindgren's group, however, has developed a rat model for dyskinesia, in which behaviour as well as molecular changes in the brain can be studied.

As is the case with humans with Parkinson's Disease, only some rats develop dyskinesia. The first part of Hanna Lindgren's thesis shows that dyskinetic rats have a larger amount of new blood vessels in the brain compared to non-dyskinetic animals. This may affect the passage of L-DOPA from blood to brain, leading to large variations in the levels of L-DOPA, which may affect the brain cells negatively.

In the second part of her thesis, Hanna Lindgren found that dyskinetic animals have a higher density of nerve projections from the brain cells that produce serotonin, another transmitter substance. These cells can help convert L-dopa into dopamine.

By changing the activity of the serotonin-producing cells, she could decrease the amount of dopamine in the rats' brains, which also decreased the dyskinesia.

– Even though we need dopamine to move, levels that are too high are no good. On the contrary, high levels are directly related to dyskinesia, says Hanna Lindgren.

What plans do you have now?
– I will stay here for another month, possibly longer, as I have some projects to finish. After that I don't know where I will end up, but I'll continue in the field of research. I have decided to do a post-doc, but I'm not sure where.

Hanna Lindgren defends her thesis Presynaptic mechanisms in L-Dopa-induced dyskinesia on Friday, 20th of March at 9.15 a.m. in Segerfalksalen, Wallenberg Neurocentrum. Faculty opponent: Director Etienne Hirsch, Lausanne. Chairman: Professor Patrik Brundin.