Since the late 80s it has been repeatedly shown that besides dopaminergic neurons, the brain contains so-called monoenzymatic neurons possessing one of the enzymes of dopamine (DA) synthesis, tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC). However, the data on the existence of monoenzymatic neurons in the striatum remain controversial, and little is known about their functional significance. The aim of this study was to test our hypothesis that monoenzymatic TH-containing neurons produce DA in cooperation with the neurons containing AADC, which might help to compensate DA deficiency under the failure of the nigrostriatal dopaminergic system. Using a combination of techniques: retrograde tracing, qPCR and immunolabeling for TH, AADC and MAP2, we showed that the striatum of mice with normal and degraded dopaminergic system comprises of monoenzymatic TH- and AADC-containing neurons. To provide evidence for cooperative synthesis of DA, we used an ex vivo model of inhibiting of DA synthesis by blocking transport of L-DOPA, produced in monoenzymatic TH-containing neurons, to neurons containing AADC by means of L-leucine, a competitive inhibitor of the membrane transporter of large neutral amino acids, and L-DOPA. With this original approach, cooperative synthesis of DA in the striatum was proven in MPTP-treated mice but not in the control. Furthermore, we demonstrated that the proportion of DA produced through cooperative synthesis in the striatum of MPTP-treated mice increases as the degradation of dopaminergic system proceeds. An increase in the proportion of cooperative synthesis of DA alongside degradation of the dopaminergic system is also proved by an increase of both TH gene expression and the number of TH-immunoreactive structures in the striatum. Thus, these data suggest that the cooperative synthesis of DA in the degraded striatum is an up-regulated compensatory reaction, which plays an increasing role as DA deficiency rises, and might be considered among the principal mechanisms of neuroplasticity in neurodegenerative diseases.
The human motor cortex is involved in the planning and execution of movements as well as in the processing of action language, and it is impaired in Parkinson's disease (PD) as a consequence of dopamine degeneration. The aim of this study is to understand the role of dopamine in the processing of action words by looking at PD patients with and without medication. A group of 23 healthy controls and 34 non-demented PD patients participated in an action verbal fluency task on and off dopamine medication. A repeated measures 2 × 2 ANOVA was conducted with dopamine (on/off) and type of verb (high and low specificity motor verbs) as independent variables and the number of words generated as a dependent variable. Our results showed that patients on dopamine medication produced a significantly greater number of high specificity motor verbs than low ones. In contrast, patients off dopamine medication generated a similar number of verbs with high and low motor specificity. MANOVA analyses showed a significantly lower production of verbs with high motor specificity on PD patients off medication compared to healthy controls. However, performance of PD patients in the on condition was similar to that found in healthy controls. In conclusion, the dopamine network from basal ganglia to brain motor areas might play a role in retrieving action verbs with specific semantic representations.