Transcriptional and structural plasticity of tyrosine hydroxylase expressing neurons in both striatum and nucleus accumbens following dopaminergic denervation

Abstract

Mice that express green fluorescent protein (GFP) under the control of tyrosine hydroxylase (TH) gene promoter were used to visualize transcriptional as well as structural regulation of TH cells following prolonged dopaminergic denervation.A unilateral lesion of the medial forebrain bundle was induced by 6-hydroxydopamine. In the unlesioned contralateral striatum and nucleus accumbens surprisingly high numbers of resident GFP-positive neurons (about 2653 and 422 per striatum and accumbens, respectively) were observed while only much lower TH-positive neurons (about 214 and 102 per striatum and accumbens, respectively) were detectable. In the lesioned hemisphere the number of GFP neurons was slightly increased already at day 4 by 16% and more at day 40 by 47% while the number of TH-immunoreactive neurons was dramatically increased by 848% at day 4 and by 1139% at day 40 over the control side. Additionally and particularly pronounced in the nucleus accumbens, GFP-positive neurons demonstrated increased sprouting of their projections over time, stronger than observed by TH-immunostaining.The load in TH protein may be essentially determined by post-transcriptional suppression/degradation while GFP may rather reflect the gross transcriptional activity. Thus, permanent dopaminergic pathway injury induces both transcriptional as well as structural plasticity of TH expressing neurons in striatal and accumbal target areas of ventral midbrain dopaminergic neurons.