Striatal neuropeptides associated with L-DOPA-induced dyskinesia
Parkinson's disease (PD) is the most common neurodegenerative disease, with approximately 6 million sufferers in the world. The patients are usually diagnosed between the ages 50-70 years and as the disease progress more symptoms may occur. The cause of the disease is unknown, but the characteristic of PD is that it is a selective degeneration of dopaminergic neurons in the substantia nigra, which leads to an absence of dopamine release in striatum. This affects the motor system of the central nervous system, resulting in a movement disorder. It is not until 70% of the dopamine neurons have been lost that the patient will show the first symptoms of the disease. This will thereby complicate the treatment of the disease. When the motor symptoms are established, it is extremely difficult to stop or reverse the disease. The most effective treatment of patients with Parkinson's disease is L-DOPA that is converted to dopamine in the brain. Dopamine agonists have also been used as a treatment alternative in PD in attempts to avoid the motor symptoms. However, everyone who gets Parkinson's disease will eventually be required to start using L-DOPA as the disease worsen and dopamine agonists loses in efficacy. The majority of patients being treated with L- DOPA have disturbing adverse reactions during the treatment as involuntary, abnormal movements, known as dyskinesias may develop. Once you have got dyskinesias it will not disappear and cannot be effectively alleviated, and will therefore often impair the person's daily life. It is therefore a major focus in research to find new treatments focused on L-DOPA induced side-effects. In a previous study several unknown neuropeptides has been detected, which might have a strong correlation between the L-DOPA and dyskinesia. The main purpose of this study is to identify these neuropeptides and locate them in the striatum of high and low dyskinetic rats. This was performed by using MALDI imaging mass spectrometry and the computer program FlexImaging that provides a visualization of peptides and proteins and their distribution in tissue sections. Of the 76 peptide families that were found in rat brains, 33 of them were identified in this study, and some of them proved to be of high interest. From these 33, three neuropeptides; corticoliberin, P3(42) and cholecystokinin-39, were chosen for further investigation. We saw elevated levels of these three in both high and low dyskinetic rats. We were able to verify with antibodies their localization in normal brains in the striatum and hippocampus. In the future, these peptides will be studied in dyskinetic rats to verify if they are significantly elevated in dyskinetic animals. These three peptides together with the other identified peptides are very interesting in hopes to be able to cure or ameliorate L- DOPA-induced dyskinesias.