Changes in metabotropic glutamate receptor 1-8 gene expression in the rodent basal ganglia motor loop following lesion of the nigrostriatal tract.
Metabotropic glutamate (mGlu) receptors in the basal ganglia motor loop may increase cell excitability (Group I) or modulate neurotransmitter release (Group I, II and III). Nigrostriatal tract degeneration in Parkinson's disease (PD) produces downstream pathological disturbances in glutamate and GABA transmission. The present study examined whether changes in mGlu receptor gene expression may either contribute to, or compensate for these pathological changes in transmission. In situ hybridisation studies examined the levels of mGlu receptor mRNA in motor loop regions in rats bearing a 6-hydroxydopamine-induced unilateral nigrostriatal tract lesion. Gene expression was reduced in the lesion compared to intact hemispheres for mGlu(1) in the substantia nigra pars compacta (SNc; 51.8+/-11.5%), mGlu(3) in the striatum and globus pallidus (11.7+/-2.8% and 18.9+/-1.4%, respectively) and mGlu(4) in the striatum and premotor cortex (13.8+/-2.7% and 15.8+/-5.5%, respectively). Loss of mGlu(1) mRNA in the SNc confirms that mGlu(1) is highly expressed on dopaminergic neurones where it may contribute to their vulnerability in PD. The down-regulation of mGlu(3) and mGlu(4) mRNA may reflect reduced transcriptional activity in response to increased levels of extracellular glutamate in these regions under parkinsonian conditions. These changes are likely to exacerbate the pathophysiological glutamate and GABA transmission within these regions in PD.
Messenger
M J
MJ
Neurodegenerative Disease Research Group, Wolfson Centre for Age-Related Diseases, King's College London, Hodgkin Building, Guy's Campus, London, SE1 1UL, UK.
Dawson
L G
LG
Duty
S
S
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D009434:Neural Pathways / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis* / Q000235:genetics*; D013378:Substantia Nigra / Q000378:metabolism*
D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C113897:metabotropic glutamate receptor 6; C102719:metabotropic glutamate receptor 7; C111435:metabotropic glutamate receptor 8; C104077:metabotropic glutamate receptor type 1; C108823:metabotropic glutamate receptor 4