Changes in gene expression of tyrosine hydroxylase, its regulating transcription factors, dopamine receptors in striatal neurons after their dopaminergic denervation

Among the priorities in neurology is the development of pathogenetic treatment for Parkinson’s disease (PD). Striatal neurons capable of expressing the tyrosine hydroxylase gene ( Th ) and containing this enzyme represent a potential target for such therapy. Transgenic mice with the green fluorescent protein gene under the Th promoter were used to model PD via 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine neurotoxin. We aimed to determine whether reduced dopaminergic innervation of the striatum is accompanied by changes in the expression of Th and genes for transcription factors regulating its expression. Twelve hours after neurotoxin administration, one‑third of dopaminergic fibers were lost, especially around Th ‑expressing neurons, while the number of Th ‑expressing neurons increased 1.4‑fold. Along with increased Th expression, expression of gene for transcription factor Nurr1 rose 4‑fold, whereas the expression of Pou2f2 gene decreased twofold. The c‑Fos gene expression doubled, while c‑Jun (which, together with c‑Fos, forms the AP‑1 transcription factor) remained unchanged. In addition to characterizing the innervation of Th ‑expressing striatal neurons, this study highlights Nurr1, AP‑1, and Pou2f2 as potential molecular targets for future research aimed at understanding Th regulation and the role of these neurons in preserving striatal dopamine levels upon deafferentation.