Effect of unilateral lesion of the nigrostriatal dopamine pathway on survival and neurochemistry of parafascicular nucleus neurons in the rat--evaluation of time-course and LGR8 expression.
In Parkinson's disease (PD), the centromedian-parafascicular nucleus of the thalamus undergoes degeneration, and a similar pattern of neurodegeneration is observed in the intralaminar parafascicular nucleus (Pf) after lesions of the nigrostriatal dopamine system in rat and mouse. The receptor for insulin-like peptide-3 (INSL3) - leucine-rich repeat containing G-protein coupled receptor 8 (LGR8)--is enriched in Pf neurons and their projections to striatum and cortex in rat brain, suggesting it as a potential marker for changes in Pf neuron function in experimental models of PD. Vesicular glutamate transporter-2 (vGlut2) expression has also been shown to reflect functional alterations in thalamic neurons. This study examined time-related effects of unilateral 6-hydroxydopamine (6-OHDA) lesions of substantia nigra (SN) on the loss/survival of Pf neurons and possible alterations in their Lgr8 and vGlut2 mRNA expression. Groups of rats with a 6-OHDA lesion or no lesion ('control') were killed after 1 and 5 months. Qualitative assessments revealed marked neuronal loss in the dorsolateral, ventrolateral and ventromedial (but not ventrolateral) Pf on the ipsilateral side to the SN lesion after 1 and 5 months. X-ray film autoradiograms of regional Lgr8 and vGlut2 mRNA densities detected by in situ hybridization were consistent with the lower ipsilateral neuron density. Nuclear emulsion detection of cellular levels of Lgr8 and vGlut2 mRNAs revealed that after 1 month, Lgr8 mRNA levels (grains/microm(2)) were decreased significantly relative to control in surviving neurons in the dorsolateral, ventrolateral ventromedial and medial Pf ipsilateral to the SN lesion, and in the dorsolateral and ventrolateral Pf contralateral to the lesion, with fewer differences in expression in cells in these areas after 5 months, suggesting a possible recovery of 'normal' activity. In contrast, no consistent changes were observed in vGlut2 mRNA levels in Pf ipsilateral and contralateral to the nigral lesion cf. control. These studies confirm the influence of midbrain dopamine systems on Pf neurons and suggest that LGR8 could be a useful marker for following changes in Pf neuron activity and adaptation under physiological modulatory and pathological conditions.
Sedaghat
Katayoun
K
Howard Florey Institute, The University of Melbourne, Victoria, Australia.
Finkelstein
David I
DI
Gundlach
Andrew L
AL