Dopamine Synthesis by Non-Dopaminergic Neurons as an Effective Mechanism of Neuroplasticity

In addition to dopaminergic (DAergic) neurons, which possess all of the enzymes of dopamine synthesis (DA), there are neurons that express only one of the enzymes, tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AAAD). These so-called monoenzymatic neurons are widely distributed in the brain and, in some areas, are even more numerous than dopaminergic (DAergic) neurons. Using in an vitro experimental approach that we developed it was first demonstrated that monoenzymatic neurons that contain complementary enzymes of DA synthesis, TH and AAAD, co-synthesize DA. L-3,4-dihydroxyphenylalanine (L-DOPA), which is synthesized from L-tyrosine in monoenzymatic TH-containing neurons, is transferred to monoenzymatic AAAD-containing neurons, where L-DOPA is converted to DA. We have also shown that cooperative synthesis of DA, although performed in some parts of the brain in the norm, is predominantly a manifestation of neuroplasticity in pathology. This additional source of DA synthesis contributes to compensation of the DA deficit, which occurs in neurodegenerative diseases such as hyperprolactinemia and Parkinson’s disease, whose pathogenesis is associated with degeneration of dopaminergic (DAergic) neurons. It is also possible that L-DOPA, which is secreted by monoenzymatic TH-containing neurons, plays the role of a neurotransmitter or neuromodulator and acts on target neurons through receptors to L-DOPA, DA, and norepinephrine. Thus, numerous non-dopaminergic monoenzymatic neurons, which are widely distributed in the brain, jointly synthesize DA, which is the most important mechanism of neuroplasticity; this compensates for the DA deficit during the degeneration of DAergic neurons.