Dopamine and serotonin metabolism in the striatum of the chronic Parkinson's disease mouse model

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease, the key pathogenetic feature of which is considered to be the degeneration nigrostriatal dopaminergic neurons and the decrease in striatal dopamine (DA) levels. The study aimed to assess the dynamic changes in the levels of DA, serotonin, and their main metabolites in the striatum of C57BL/6 mice with the chronic toxic PD model induced by administration of multiple doses of 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) combined with probenecid. The use of such modeling protocol enables simulation of the long-lasting neurochemical alterations similar to the slow progressive course of the disease in humans. Neurotransmitters and their metabolites were quantified by high-performance liquid chromatography with electrochemical detection. The study results demonstrate the decrease in the total DA metabolism in both axon terminals and the synaptic cleft during early neurodegeneration typical for PD. The most pronounced decrease in the levels of DA and its metabolite DOPAC was observed a week after the course of MPTP/ probenecid injections: it was 36% and 32% of the control level, respectively. It is noteworthy that the DA and DOPAC levels remained decreased throughout 3 months and were restored to the control level as late as 6 months after the end of the course of MPTP/probenecid injections. In general, the model presented makes it possible to extend the window of neurodegenerative alteration manifestation to 3 months. The data obtained once again demonstrate a complex pattern of the effects of neurodegenerative and compensatory processes occurring at the earliest stages of neurodegeneration in PD.