Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.9.3.1 (cytochrome oxidase)
8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GABA and glutamate decarboxylase (GAD) immunoreactivities were examined in dorsal lateral geniculate nuclei (LGN) of normal monkeys (Macaca fascicularis) and in monkeys that had one eye injected with tetrodotoxin (TTX) or one eye removed 5 days to 4 weeks prior to sacrifice. As seen in previous studies (Wong-Riley and Carroll 1984) monocular TTX injections or enucleation quickly reduced cytochrome oxidase (CO) staining in layers 2, 3 and 5 of the ipsilateral LGN and in layers 1, 4 and 6 of the contralateral LGN. The reduction in CO staining was apparent at all survival times examined. By contrast, GABA and GAD immunostaining in the LGNs were qualitatively normal up to two weeks following enucleation or after 17 days of TTX injections. Quantitative and stereological analyses confirmed that the numerical density and proportion of GABA and GAD neurons do not change in the LGN following two weeks of denervation or deprivation, even though in the same monkeys a reduction in GABA immunostaining was found in deprived-eye columns of area 17. However, with longer survivals, of 3-4 weeks in duration, the number of GABA and GAD immunostained neurons in the deprived/denervated-eye laminae of the LGN was reduced by one-third. These findings demonstrate that the deprivation-induced reduction in GABA and GAD immunoreactivity is delayed in the LGN, by comparison with the visual cortex, and suggest that the effects in the LGN may be relayed through the cortex or that neurotransmitter levels may be regulated by different mechanisms in the two sites.
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PMID:Delayed reduction in GABA and GAD immunoreactivity of neurons in the adult monkey dorsal lateral geniculate nucleus following monocular deprivation or enucleation. 175 98

A new approach to high-resolution 2-deoxy-D-glucose (2DG) emulsion-autoradiography which combines improved retention of 2DG labeling, staining with immunohistochemical and other specific markers, and automated data collection and analysis of local silver grain and stain densities is described. The Durham et al. (J. Neurosci. 1:519-526, '81) procedure for fixation of 2DG with periodate-lysine-paraformaldehyde (PLP, McLean and Nakane: J. Histochem. Cytochem. 22:1077-1083, '74) was adapted to increase retained label roughly tenfold. Phenobarbital anesthesia is induced 45 minutes after 2DG injection. Barbiturate anesthesia increases brain glycogen (Nelson et al.: J. Neurochem. 15:1271-1279, '68) and presumably increases the incorporation of intracellular 2DG from 2DG-6P into brain glycogen and other molecules (Nelson et al.: J. Neurochem. 43:949-956, '84; Pentreath et al.: Neuroscience 7:759-767, '82). Iodoacetate is added to cold fixative to prevent glycogen breakdown (Cammermeyer and Fenton: Histochemistry 76:339-356, '82). This high-resolution 2DG protocol is directly compatible with many other neuroanatomical techniques. We demonstrate 2DG emulsion autoradiography combined with cytochrome oxidase (CO) histochemistry, markers for axonal pathway tracing, plastic embedding for semithin sections, and immunohistochemical staining for glutamate decarboxylase (GAD). The method should be compatible with antibodies for other antigens and with other neuroanatomical stains. To collect the data directly from microscope slides, a computer-controlled microscope was integrated with image-processing software to eliminate the need for manual counting and scoring of autoradiograms. Regions of interest are scanned automatically at high resolution to map regional labeling and/or stain density. There is excellent correspondence between computer-enhanced two-dimensional maps of the data and the original autoradiograms. Automated counts for five specimens were compared to counts of labeled cells by trained observer. The correlation between the two sets of measurements is high (r = .93). Automated data collection has been generalized to measure regional stain densities on the autoradiographed sections for direct comparison with silver grain density. The method is extremely flexible, especially since new image-processing strategies can be developed in software to extract the desired information from materials labeled by other methods (e.g., HRP).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New high-resolution 2-deoxyglucose method featuring double labeling and automated data collection. 306 65

In intact dentate gyrus, glutamate decarboxylase immunoreactivity (GAD) and cytochrome oxidase activity (CyO) showed different distributions patterns. Entorhinal lesions caused increases of GAD and CyO in the outer molecular layer (OML) of the ipsilateral side. Submicroscopical localization of these enzymes did not change, except for CyO labeling more astrocytic mitochondria. The increase in numerical density of GAD puncta correlated quantitatively with shrinkage of OML, whereas in the whole molecular layer the number of GAD puncta remained unchanged. Hence, the localized increase of enzyme activities and lysosomes is apparently related to shrinkage of OML, but does not indicate plasticity of GABAergic neurons.
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PMID:Entorhinal lesions result in shrinkage of the outer molecular layer of rat dentate gyrus leading subsequently to an apparent increase of glutamate decarboxylase and cytochrome oxidase activities. 631 99

The maximal rate of some cerebral enzymatic activities related to energy transduction (hexokinase; phosphofructokinase; lactate dehydrogenase; citrate synthase; malate dehydrogenase; total NADH-cytochrome c reductase; cytochrome oxidase), amino acid metabolism (glutamate decarboxylase; glutamate dehydrogenase) and cholinergic metabolism (acetylcholine esterase) were tested in the cerebral cortex and in sub-cortical area of rats. The evaluations were performed both in the homogenate in toto and in the crude mitochondrial fraction, before and after a postdecapitative normothermic ischemia of 5, 10, 20, and 40 min duration. The results are discussed also with respect to the pharmacological pretreatment with two biological substances which may modulate amino acid (L-alanine) and phospholipid metabolism (CDP-choline). The analysis of the present data suggests the occurrence in brain tissue of a variety of interrelated factors implicated in the ischemia-induced changes of the maximal rate of the enzymatic activities related to the energy transduction. These include: (a) rearrangement of the enzymatic activities because of the changed metabolic and chemico-physical condition; (b) decrease in the activity of enzymes related to the electron transfer chain and glycolysis; (c) changes in enzymes related to mitochondrial membranes. The effects of in vivo administration of alanine or CDP-choline, even if significant, are not consistent throughout the time period studied.
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PMID:Changes induced by ischemia on some cerebral enzymatic activities related to energy transduction and amino acid metabolism. 685 30

The postnatal development of direct thalamocortical projections from the zona incerta of the ventral thalamus to the whisker representation area of the rat primary somatosensory cortex was investigated. Cytoarchitectonic analysis based on Nissl staining, cytochrome oxidase histochemistry and immunohistochemistry for glutamic acid decarboxylase, GABA, parvalbumin and calbindin D28K revealed that the zona incerta can be clearly distinguished from surrounding diencephalic structures from the day of birth. Moreover, four distinct anatomical subdivisions of this nucleus were identified: the rostral, dorsal, ventral and caudal. Of these, the ventral subdivision is by far the most conspicuous, containing the highest density of neurons, and the highest levels of cytochrome oxidase, glutamate decarboxylase, GABA, parvalbumin and calbindin D28K. In contrast, the dorsal, rostral and caudal subdivisions contain fewer cells, lower levels of glutamic acid decarboxylase and GABA and very few parvalbumin-positive and calbindin-positive neurons. Small injections of rhodamine coated microspheres or Fluoro-gold in the primary somatosensory cortex of animals at different stages of development revealed the existence of retrogradely labeled neurons in the rostral and dorsal subdivisions of the zona incerta from postnatal day 1. At this age, retrogradely labeled cells were also found in the ventral lateral, ventral posterior medial, posterior medial, centrolateral, ventral medial and magnocellular subdivision of the medial geniculate nuclei of the dorsal thalamus. The density of the incertocortical projection reaches its maximum between the first and second postnatal weeks, decreasing subsequently, until an adult pattern of labeling is achieved. Tracer injections combined with immunohistochemistry revealed that the majority of the incertocortical projection derives from GABAergic neurons, implying a potentially inhibitory role for the incertocortical projection. These results demonstrate that the rat trigeminal system contains parallel thalamocortical pathways of opposite polarity, emerging from both the dorsal (glutamatergic, excitatory) and ventral (GABAergic, inhibitory) thalamus since the day of birth. As such, these findings suggest that, contrary to the classical notion, not only the dorsal but also the ventral thalamus may play a special role in both cortical maturation and function.
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PMID:Development of direct GABAergic projections from the zona incerta to the somatosensory cortex of the rat. 777 73

Recent pathophysiological models of basal ganglia function in Parkinson's disease predict that specific neurochemical changes in the indirect pathway would follow the lack of stimulation of D(2) dopamine receptors. Post mortem studies of the basal ganglia in genetically modified mice lacking functional copies of the D(2) dopamine receptor gene allowed us to test these predictions. When compared with their congenic N(5) wild-type siblings, mice lacking D(2) receptors show an increased expression of enkephalin messenger RNA in the striatum, and an increased activity and expression of cytochrome oxidase I in the subthalamic nucleus, as expected. In addition, D(2) receptor-deficient mice display a reduced expression of glutamate decarboxylase-67 messenger RNA in the globus pallidus, as the basal ganglia model predicts. This reduction contrasts with the lack of change or increase in glutamate decarboxylase-67 messenger RNA expression found in animals depleted of dopamine after lesions of the mesostriatal dopaminergic system. Furthermore, D(2) receptor-deficient mice show a significant decrease in substance P messenger RNA expression in the striatonigral neurons which form the direct pathway. Finally, glutamate decarboxylase-67 messenger RNA expression in the basal ganglia output nuclei was not affected by mutations in the D(2) receptor gene, a fact that could probably be related to the absence of a parkinsonian locomotor phenotype in D(2) receptor-deficient mice. In summary, these findings provide compelling evidence demonstrating that the lack of endogenous stimulation of D(2) receptors is sufficient to produce subthalamic nucleus hyperactivity, as assessed by cytochrome oxidase I histochemistry and messenger RNA expression, and strongly suggest the existence of interactions between the basal ganglia direct and indirect pathways.
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PMID:The indirect basal ganglia pathway in dopamine D(2) receptor-deficient mice. 1097 27

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

The long-duration response (LDR) is a sustained improvement in parkinsonism due to chronic levodopa therapy and lasts after discontinuation of treatment. We have investigated the molecular changes that underlie the LDR in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion. Animals were treated for 22 days with levodopa or saline. Forelimb akinesia was evaluated prior and following a test dose of levodopa. Rotational behaviour was weekly evaluated. Levodopa induced an improvement in the parkinsonian limb akinesia that lasted for 48 h after withdrawal. A shortening in the duration of rotational behaviour was observed. After 3 days of washout, levodopa treatment maintained elevated striatal preproenkephalin mRNA expression, also inducing an increase in preprodynorphin (PDyn) and dopamine D-3 receptor mRNAs, but without any modification of the adenosine A(2A) mRNA expression induced by 6-OHDA. Levodopa reversed the lesion-induced increase in the expression of cytochrome oxidase mRNA in the subthalamic nucleus and glutamate decarboxylase mRNA in the pars reticulata of the substantia nigra. After 7 days of levodopa washout, the molecular markers show a decline in the basal ganglia evolving towards the parkinsonian state, being statistically significant for the striatal PDyn mRNA. This study characterizes the concomitant presence of the short-duration response and LDR to levodopa in the 6-OHDA model of parkinsonism and shows that the molecular changes induced by levodopa in the basal ganglia are not permanent and that this reversal after levodopa washout may be responsible for the gradual motor deterioration that characterize the LDR.
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PMID:Concomitant short- and long-duration response to levodopa in the 6-OHDA-lesioned rat: a behavioural and molecular study. 1724 Dec 87

Brain mitochondria are relatively resistant to calcium-induced mitochondrial permeability transition (MPT), with heterogenic response to the insult. The cause for this heterogeneity is not clear, so we studied the distribution of a key regulator of the MPT, cyclophilin D (cypD), within the rat brain by using immunohistology and Western blotting. Motor and parietal cortex, hippocampus, striatum, substantia nigra, ventral tegmental area, septum, and mammillary nucleus displayed a strong immunoreactivity to cypD within specific subpopulation of neurons. The staining was punctate and intense, particularly in perinuclear regions of cells. Apart from neurons, a subpopulation of astrocytes and NG2-positive cells showed higher cypD immunoreactivity. Double staining of cypD with cytochrome oxidase confirmed the mitochondrial specificity of cypD immunoreactivity. The neurons with high levels of cypD also expressed glutamate decarboxylase (GAD) and the calcium binding protein parvalbumin or calbinding D-28k, identifying these cells as interneurons. Western blots confirmed our immunohistochemical findings, showing significantly higher levels of cypD in crude mitochondria of substantia nigra compared with cortex or striatum. Furthermore, nonsynaptic mitochondria representing mainly mitochondria from cell bodies of neurons and glia have about 16% higher levels of cypD compared with synaptic mitochondria that are localized in presynaptic buttons. These data suggest that the underlying factor of heterogenic response of isolated brain mitochondria to MPT-inducing insults can be the different expression levels of cypD, with mitochondria originated from interneurons as the most sensitive.
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PMID:Cyclophilin D is expressed predominantly in mitochondria of gamma-aminobutyric acidergic interneurons. 1895 28

We investigated the effect of early vs. late initiation of levodopa treatment on dyskinetic movements, rotational behavior and molecular markers in hemiparkinsonian rats. Male Sprague-Dawley rats received a unilateral 6-hydroxydopamine (6-OHDA) administration in the nigrostriatal pathway. Rats were divided into three groups treated with: (i) levodopa (6 mg/kg) twice daily for 22 days starting at 4 weeks after 6-OHDA (Early group); (ii) levodopa at the same dose, regimen and duration but starting at 12 weeks after 6-OHDA (Late group), and (iii) saline starting at 4 weeks after 6-OHDA and continuing until the Late group finished treatment. Dyskinesias were quantified on days 1 and 22 of levodopa treatment. Striatal expression of preproenkephalin and preprodynorphin mRNAs, subthalamic cytochrome oxidase mRNA, and glutamate decarboxylase 67 mRNA in the pars reticulata of the substantia nigra was measured by in-situ hybridization. After 22 days of levodopa treatment, the percentage of rats showing dyskinesia was lower in the Early group than in the Late group (60% vs. 100%, respectively). No significant differences in total dyskinesia score were observed between both groups with the exception of the orolingual dyskinesias that were significantly less frequent in the Late group (P < 0.01). No significant differences were observed in the molecular markers between the Early and Late groups. Prompt initiation of levodopa treatment might be able to delay some of the basal ganglia molecular and circuitry changes underlying the development of dyskinesia but, once developed, they are behaviorally and molecularly similar to those appearing after late initiation of levodopa.
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PMID:Effects of early vs. late initiation of levodopa treatment in hemiparkinsonian rats. 1971 1


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