title: Changes in GABA(B) receptor mRNA expression in the rodent basal ganglia and thalamus following lesion of the nigrostriatal pathway.
abstract: Loss of striatal dopaminergic innervation in Parkinson's disease (PD) is accompanied by widespread alterations in GABAergic activity within the basal ganglia and thalamus. Accompanying changes in GABA(B) receptor binding have been noted in some basal ganglia regions in parkinsonian primates, suggesting that plasticity of this receptor may also occur in PD. However, the molecular mechanisms underlying the changes in receptor binding and the manner and extent to which different GABA(B) receptor mRNA subunits and splice-variants are affected remain unknown. This study used in situ hybridisation to examine the full profile of changes in expression of the known rat GABA(B) receptor genes and gene variants in the basal ganglia and thalamus of rats, brought about by degeneration of the nigrostriatal tract. All of the GABA(B) mRNA species examined showed unique expression patterns throughout the basal ganglia and thalamus. In addition, all exhibited a marked loss of expression (between 46 and 80%) in the substantia nigra pars compacta of animals bearing a complete 6-hydroxydopamine-induced lesion of the nigrostriatal tract, confirming the presence of these variants in dopaminergic neurones in this region. Further analysis of autoradioagrams revealed additional changes only in GABA(B(1a)) mRNA in discrete anatomical regions. Expression of the GABA(B(1a)) variant was significantly increased in the substantia nigra pars reticulata (33+/-2%), entopeduncular nucleus (26+/-1%) and the subthalamic nucleus (16+/-1%). Since these regions all receive reduced GABAergic innervation following nigrostriatal tract lesioning, it is possible that the increased expression occurs as a compensatory measure. In conclusion, these data demonstrate that GABA(B) receptor genes exhibit regional- and subunit/variant-specific plasticity at the molecular level under parkinsonian conditions.
authors.affiliation: Neurodegenerative Disease Research Group, Wolfson Centre for Age-Related Diseases, Hodgkin Building, King's College London, Guy's Campus, SE1 1UL, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Johnston
authors.forename: S
authors.initials: S
authors.lastname: Duty
mesh_terms: D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000378:metabolism*; D003720:Densitometry; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D008454:Mazindol / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects; D015345:Oligonucleotide Probes; D016627:Oxidopamine / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects; D013788:Thalamus / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism
chemical_list: D018765:Dopamine Uptake Inhibitors; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D018080:Receptors, GABA-B; D014316:Tritium; D016627:Oxidopamine; D008454:Mazindol