Tyrosine Hydroxylase, Vesicular Monoamine Transporter and Dopamine Transporter mRNA Expression in Nigrostriatal Tissue of Rats with Pedunculopontine Neurotoxic Lesion

Abstract

Background: The degeneration of the pedunculopontine nucleus (PPN) precedes the degeneration of the nigral cells in the pre-symptomatic stages of Parkinson’s disease (PD). Although the literature recognizes that a lesion of the PPN increases the vulnerability of dopaminergic cells, it is unknown if this risk is associated with the loss of capability of handling the dopaminergic function. Methods: In this paper, the effects of a unilateral neurotoxic lesion of the PPN in tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) mRNA expression in nigrostriatal tissue were evaluated. Three experimental groups were organized: non-treated rats, NMDA-lesioned rats and Sham-operated rats. Results: Seven days after the PPN lesion, in nigral tissue, TH mRNA expression was higher in comparison with control groups (p < 0.05); in contrast, VMAT2 mRNA expression showed a significant decrease (p < 0.01). DAT mRNA expression showed a significant decrease (p < 0.001) in the striatal tissue. Comparing nigral neuronal density of injured and control rats revealed no significant difference seven days post-PPN injury. Conclusions: Findings suggest that the PPN lesion modifies the mRNA expression of the proteins associated with dopaminergic homeostasis at nigrostriatal level. It could represent vulnerability signals for nigral dopaminergic cells and further increase the risk of degeneration of these cells.

Motor Coordination Disorders Evaluated through the Grid Test and Changes in the Nigral Nrf2 mRNA Expression in Rats with Pedunculopontine Lesion

“…This temporal behavior may be part of a mosaic of molecular events that involves the nigral gene expression of other genes, such as: the brain derived neurotrophic factor , key in the survival of nigral dopaminergic neurons, TH , VMAT and DAT , essential in maintaining dopaminergic homeostasis, as well as Nurr1 and Pitx3 , those that play a role in maintaining the dopaminergic phenotype [ 10 , 11 , 12 ].…”

“…On the other hand, our group demonstrated an increase in the TH mRNA expression together with a decrease in the VMAT mRNA expression in nigral tissue, seven days after PPN lesion [ 11 ]. This combination was considered an early signal of alarm for the nigral dopaminergic neurons.…”

“…This combination was considered an early signal of alarm for the nigral dopaminergic neurons. Even if higher levels of dopamine were being synthesized, the dopamine vesicular storage would be compromised in this situation [ 11 ]. Vesicular packing prevents the cytosolic accumulation of DA and its subsequent oxidation to potentially neurotoxic molecules [ 53 ].…”

“…Our group has published evidence supporting the concurrence of events that increase the risk to nigral degeneration together with molecular and biochemical changes, suggesting compensatory mechanisms at nigral level in rats with a neurotoxic lesion of PPN [ 9 , 10 , 11 , 12 ]. In this sense, our results showed the occurrence of oxidative stress events at the nigrostriatal level, concomitant with a decrease in the nigrostriatal mRNA expression of vesicular monoamine transporters (VMAT2) and the dopamine transporter (DAT) in PPN-lesioned rats [ 9 ].…”

“…In this sense, our results showed the occurrence of oxidative stress events at the nigrostriatal level, concomitant with a decrease in the nigrostriatal mRNA expression of vesicular monoamine transporters (VMAT2) and the dopamine transporter (DAT) in PPN-lesioned rats [ 9 ]. In connection with the compensatory mechanisms, our finding demonstrated an increase in the mRNA expression of brain-derived neurotrophic factor (BDNF) and tyrosine hydroxilase (TH), together a slight increase in gluthatione (GSH) level in nigral tissue of rats with PPN injury [ 10 , 11 ].…”