Intralaminar thalamic nuclei lesions: widespread impact on dopamine denervation-mediated cellular defects in the rat basal ganglia.
Intralaminar thalamic nuclei represent a major site of non-dopaminergic degeneration in Parkinson disease, but the impact of this degeneration on the pathophysiological functioning of basal ganglia remains unknown. To address this issue, we compared the effects of 6-hydroxydopamine-induced lesions of nigral dopamine neurons alone or combined with ibotenate-induced lesions of intralaminar thalamic neurons on markers of neuronal metabolic activity in the rat basal ganglia using in situ hybridization histochemistry. Thalamic lesions prevented most of the dopamine denervation-induced changes (i.e. the increases in mRNA levels of enkephalin and GAD67 in the striatum, of GAD67 in the globus pallidus and entopeduncular nucleus, and of cytochrome oxidase subunit-I in the subthalamic nucleus), but did not affect the downregulation of striatal substance P and upregulation of GAD67 in the substantia nigra pars reticulata. We also provide immunohistochemical evidence that thalamic lesions markedly decreased striatal expression of the vesicular glutamate transporter vGluT2, confirming the association of this transporter with the thalamic projections to the basal ganglia. Altogether, these data reveal a major antagonistic influence of thalamic and dopaminergic afferents onto the basal ganglia and suggest that degeneration of thalamic neurons in Parkinson disease may represent an important factor counteracting expression of the defects associated with the dopamine denervation.
Bacci
Jean-Jacques
JJ
Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, Centre National de la Recherche Scientifique, Marseille, France.
Kachidian
Philippe
P
Kerkerian-Le Goff
Lydia
L
Salin
Pascal
P
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D005968:Glutamate Decarboxylase / Q000096:biosynthesis / Q000187:drug effects; D007051:Ibotenic Acid / Q000494:pharmacology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020646:Intralaminar Thalamic Nuclei / Q000187:drug effects / Q000473:pathology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000187:drug effects; D026901:Membrane Transport Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000096:biosynthesis / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000473:pathology; D013563:Sympathectomy, Chemical; D050599:Vesicular Glutamate Transport Protein 2; D033921:Vesicular Transport Proteins
D018663:Adrenergic Agents; D002352:Carrier Proteins; D007527:Isoenzymes; D026901:Membrane Transport Proteins; D009479:Neuropeptides; C493475:Slc17a6 protein, rat; D050599:Vesicular Glutamate Transport Protein 2; D033921:Vesicular Transport Proteins; D007051:Ibotenic Acid; D016627:Oxidopamine; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D004298:Dopamine