There is growing interest for trace amines, which are present in low amounts in the brain. Trace amines activate TAAR-1 receptors, which modulate D2 dopamine receptors. The coordinating Unit will collaborate with the Unit of Prof. Alemà for the study of trace amines and TAAR-1 receptors in the MPTP mouse model of parkinsonism. Mice will be treated with either low or high doses of MPTP, and levels of trace amines and TAAR-1 receptors in the dorsal striatum and other brain regions will be determined by UPLC-MS/MS and immunoblotting, respectively. MPTP-injected mice will also be treated with L-DOPA, and trace amines and TAAR-1 will be measured in mice developing or not L-DOPA-induced dyskinesias (LIDs). Additional groups of mice will receive MPTP +/- L-DOPA combined with a partial agonist (R05263397, 3 mg/kg) or an antagonist (EPPTB, 10 mg/kg) of TAAR-1 receptors. We will determine the effect these drugs on MPTP toxicity and behavioral responses to L-DOPA. For the assessment of nigro-striatal degeneration we will measure the levels of dopamine and its metabolites in the striatum and the absolute number of TH+ neurons in the substantia nigra. We will also examine the expression of genes encoding pro- and anti-inflammatory proteins in the striatum. Behavioral analysis will be carried out by measuring locomotor activity, motor coordination, muscle strength, and LIDs. Clinical studies will be carried out by Prof. Pontieri and his team. Trace amines will be measured in the serum of naïve PD patients and compared to age-matched healthy controls. Patients will then be treated with L-DOPA to assess how this treatment affects trace amine levels. The analysis will be extended to a different group of patients under long-term treatment with L-DOPA showing motor and non-motor fluctuations and LIDs. The Unit of Prof. Pontieri will use several clinical scales for the assessment of motor and non-motor symptoms, and scores will be correlated to levels of each selected trace amine.
