Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study investigated the influence of thalamic inputs on neuronal metabolic activity in the rat basal ganglia. By means of in situ hybridization histochemistry, we examined the consequences of ibotenate-induced unilateral lesion of intralaminar thalamic nuclei on mRNA expression of cytochrome oxidase subunit-I (CoI) in the striatum and the subthalamic nucleus (STN) and of the two isoforms of glutamate decarboxylase (GAD65 and GAD67) in the striatum, globus pallidus (GP), entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr). In the striatum, GAD67 mRNA expression decreased selectively in the rostral part of the structure at 5 and 12 days postlesion (approximately -30%), whereas, GAD65 mRNA levels was downregulated only in the caudal striatum at 12 days (-29%). In both the striatum and STN, CoI mRNA expression decreased ipsilaterally at 5 and bilaterally at 12 days. In GP, GAD67 and GAD65 mRNA expression decreased ipsilaterally at 5 (-20% and -26%) and 12 days (-23% and -36%). In EP, selective bilateral decreases in GAD67 mRNA expression were found at 5 and 12 days (-50% and -40%). Conversely, in SNr, only GAD65 mRNA expression was reduced bilaterally at both time points. These data show that the thalamus exerts a widespread excitatory influence on the basal ganglia network that cannot be accounted for solely by its known direct connections. Given the recent data showing that intralaminar thalamic nuclei are a major nondopaminergic site of neurodegeneration in Parkinson's disease, these results may have a critical bearing on understanding the cellular basis of basal ganglia dysfunction in parkinsonism.
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PMID:Effects of intralaminar thalamic nuclei lesion on glutamic acid decarboxylase (GAD65 and GAD67) and cytochrome oxidase subunit I mRNA expression in the basal ganglia of the rat. 1209 98

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.
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PMID:Intralaminar thalamic nuclei lesions: widespread impact on dopamine denervation-mediated cellular defects in the rat basal ganglia. 1474 58

The subthalamic nucleus (STN) receives direct dopaminergic innervation from the substantia nigra pars compacta that degenerates in Parkinson's disease. The present study aimed to investigate the role of dopaminergic denervation of STN in the origin of levodopa-induced dyskinesias. Rats were distributed in four groups which were concomitantly lesioned with 6-OHDA or vehicle (sham) in the STN and in the medial forebrain bundle (MFB) as follows: a) MFB-sham plus STN-sham, b) MFB-sham plus STN-lesion, c) MFB-lesion plus STN-sham, and d) MFB-lesion plus STN-lesion. Four weeks after lesions, animals were treated with levodopa (6mg/kg with 15mg/kg benserazide i.p.) twice daily for 22 consecutive days. Abnormal involuntary movements were measured. In situ hybridization was performed measuring the expression of striatal preproenkephalin, preprodynorphin, STN cytochrome oxidase (CO) and nigral GAD67 mRNAs. STN 6-OHDA denervation did not induce dyskinesias in levodopa-treated MFB-sham animals but attenuated axial (p<0.05), limb (p<0.05) and orolingual (p<0.01) dyskinesias in rats with a concomitant lesion of the nigrostriatal pathway. The attenuation of dyskinesias was associated with a decrease in the ipsilateral STN CO mRNA levels (p<0.05). No significant differences between MFB-lesion plus STN-sham and MFB-lesion plus STN-lesion groups in the extent of STN dopaminergic denervation were observed. Moreover, intrasubthalamic microinfusion of dopamine in the MFB-lesion plus STN-lesion group triggered orolingual (p<0.01), but not axial or limb, dyskinesias. These results suggest that dopaminergic STN innervation influences the expression of levodopa-induced dyskinesias but also the existence of non dopaminergic-mediated mechanisms. STN noradrenergic depletion induced by 6-OHDA in the STN needs to be taken in account as a possible mechanism explaining the attenuation of dyskinesias in the combined lesion group.
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PMID:Subthalamic 6-OHDA-induced lesion attenuates levodopa-induced dyskinesias in the rat model of Parkinson's disease. 2414 May 62