Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present experiments were performed to determine whether the age-related loss of striatal D2 receptors could be localized to a kainic acid-sensitive neuronal population. This neurotoxin selectively destroys intrinsic neurons. Thus, if kainic acid reduced striatal D2 receptor concentrations such that age differences in this parameter were no longer observed, it would be a good indication that the D2 receptors lost through aging are also sensitive to kainic acid. Mature (6 months) and senescent (24 months) rats were stereotaxically, unilaterally injected with 3 micrograms/0.5 microliter kainic acid into the right striatum. Seven days later striatal D2 receptors were assessed with [3H]-spiperone in one group of mature and senescent rats. A second group of mature and senescent unilaterally lesioned rats was anesthetized and perfused. Brains were dissected and processed for striatal cell counts using cresyl violet staining, tyrosine hydroxylase and met-enkephalin using immunocytochemistry, and acetylcholinesterase using histochemistry. Age-related differences in D2-receptor concentrations were observed in intact, but not lesioned, striata. Kainic acid was less effective in reducing D2-receptor concentrations in senescent animals, suggesting that some proportion of the receptors was already lost prior to lesioning. Kainic acid also reduced total neuronal numbers, as well as Met-Enk and AChE positive staining, to approximately the same extent in mature and senescent rats. No age differences were seen in any of the other parameters following kainic acid administration.
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PMID:The deleterious effects of aging and kainic acid may be selective for similar striatal neuronal populations. 168 53

Kainic acid or 6-hydroxydopamine (6-OHDA) was injected into rat striatum, and their effects on astrocytes, laminin, and catecholamine fibers were examined temporally by immunohistochemical methods in an attempt to understand the roles of reactive astrocytes and laminin on the restoration of central nervous tissue. Kainic acid injection caused a severe neuronal degeneration in the striatum but catecholamine fibers were spared with only transient loss of tyrosine hydroxylase immunoreactivity. Reactive astrocytes appeared around the lesioned area soon after the kainic acid injection, then migrated into that area, and finally covered the lesioned striatum. Laminin immunoreactivity was found only in the lesioned area before the migration of reactive astrocytes and disappeared when the area was covered by astrocytes. 6-OHDA injection, on the other hand, resulted in a severe degeneration of catecholamine fibers, but striatal neurons were mostly spared. From 7 to 28 days after injection, regenerating fibers were found to enter the affected region. In this period reactive astrocytes were seen in the affected region but were only slightly more numerous than those found in control (saline injected) striatum. Laminin-immunoreactive blood vessels seemed to show a distribution similar to that in control striatum. These observations indicate that reactive astrocytes may play an important role in areas of neuronal cell loss and that laminin may aid their migration into such areas. Laminin and reactive astrocytes may not, however, be essential for the regeneration of dopamine fibers.
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PMID:Astroglial cell alteration caused by neurotoxins: immunohistochemical observations with antibodies to glial fibrillary acidic protein, laminin, and tyrosine hydroxylase. 257 49

Kainic acid was injected bilaterally (4.8 micrograms in 1.2 microliters each side) into the dorsolateral pontomesencephalic tegmentum of cats in order to destroy the cholinergic neurons located in that region and thus to study the effects of their destruction upon sleep-waking states. The kainic acid produced a large area of nerve cell loss and/or gliosis centered in the dorsolateral tegmentum-cholinergic cell area, that includes the pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei rostrally (A1-P2), and the parabrachial (PB) and locus coeruleus (LC) nuclei caudally (P3-P5). The mean loss of choline acetyltransferase (ChAT)-immunoreactive neurons within this area was 60% with a range from 25% to 85% across 11 cats. The mean loss of tyrosine hydroxylase (TH)-immunoreactive neurons, differentially distributed through the same region, was 35% with a range of 0-50%. Whereas the kainic acid lesions appeared to have only slight effects upon wakefulness and slow-wave sleep, they had marked effects upon paradoxical sleep (PS), which varied in degree across animals. In cats with the most extensive destruction of cholinergic neurons, PS was eliminated in the first few weeks following the lesion and then reappeared as isolated episodes characterized by sparse, low amplitude PGO spikes in association with few eye movements and an activated cortex, though in absence of neck muscle atonia. Although these PS-like episodes varied in amount, they were significantly less than baseline PS in percent and in duration for the group of 11 animals over one month recording. The PGO spike rate was significantly reduced; the EMG amplitude was significantly increased, marking a loss of neck muscle atonia. The percent of PS-like epochs, the rate of PGO spiking and the EMG amplitude on postlesion day 28 were found to be significantly correlated with the volume of the lesion within the dorsolateral pontine tegmentum-cholinergic cell area. The percent PS-like episodes and PGO spike rate were significantly correlated with the number of remaining ChAT-immunoreactive neurons, but not with the number of remaining TH-immunoreactive neurons within this region. These results suggest that cholinergic pontomesencephalic neurons may be critically involved in the generation of paradoxical sleep and its phasic events.
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PMID:Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. II. Effects upon sleep-waking states. 290 97

Kainic acid was injected bilaterally (4.8 micrograms in 1.2 microliter each side) into the dorsolateral pontomesencephalic tegmentum of cats in order to destroy cholinergic cells which are located within the pedunculopontine tegmental (PPT), laterodorsal tegmental (LDT), parabrachial (PB), and locus ceruleus (LC) nuclei in this species. The neurotoxic lesions resulted in the destruction of the majority (approximately 60%) of choline acetyltransferase (ChAT)-immunoreactive neurons and a minority (approximately 35%) of tyrosine hydroxylase (TH)-immunoreactive neurons, as well as in the destruction of other chemically unidentified neurons, in the region. The effects of these lesions upon the cholinergic innervation of the brain were investigated by comparison of brains with and without lesions which were processed for acetylcholinesterase (AChE) silver, copper thiocholine histochemistry and ChAT radio-immunohistochemistry. In the forebrain, a major and significant decrease in AChE staining, measured by microdensitometry, and associated with a decrease in ChAT immunoreactivity was found in certain thalamic nuclei, including the dorsal lateral geniculate, lateral posterior, pulvinar, intralaminar, mediodorsal and reticular nuclei. All of these nuclei receive a rich cholinergic innervation evident in both AChE histochemistry and ChAT immunohistochemistry. No significant difference in AChE staining or ChAT immunoreactivity was detected in other thalamic nuclei or in the subthalamus, hypothalamus or basal forebrain. In the brainstem, a significant decrease of AChE staining and ChAT immunoreactivity was found in the superior colliculus and the medullary reticular formation, where ChAT-immunoreactive fibers were moderately dense in the normal animal. These results indicate that the pontomesencephalic cholinergic neurons may influence the forebrain by major projections to the thalamus, involving both relay and non-specific thalamocortical projection systems, and thus act as an integral component of the ascending reticular system. They may influence the brainstem by projections onto deep tectal neurons and other reticular neurons, notably those in the medullary reticular formation, and thus also affect bulbar and bulbospinal systems.
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PMID:Neurotoxic lesions of the dorsolateral pontomesencephalic tegmentum-cholinergic cell area in the cat. I. Effects upon the cholinergic innervation of the brain. 325 79

Unilateral nigrostriatal lesions produced by injecting 6-hydroxydopamine stereotaxically into both the substantia nigra and the medial forebrain bundle reduced striatal tyrosine hydroxylase activity and dopamine (DA) concentrations by 95% (compared with the intact, contralateral striata) but lowered dopa decarboxylase (DDC) activity by only 80%. L-Dopa administration increased DA concentrations in both lesioned and unlesioned sides; absolute increases were higher in control striata and pretreatment with carbidopa (an inhibitor of peripheral DDC) amplified the increases on both sides. Animals given both of the above lesions plus intrastriatal kainic acid injections exhibited a further reduction in DDC activity, i.e., to only 6% of the activity measured in intact, contralateral striata. Kainic acid lesions alone reduced striatal DDC activity by 20%, without affecting striatal tyrosine hydroxylase activity or DA concentrations, and diminished DA formation from exogenous L-dopa. These observations indicate that DA formation from exogenous L-dopa within the striatum occurs mainly, but not exclusively, within DA terminals. Some DA formation persists after most DA neurons have been destroyed; it may occur within kainic acid-sensitive striatal interneurons or efferent neurons. The DA formed outside DA neurons is apparently able to stimulate postsynaptic DA receptors and to mediate some of the behavioral effects of L-dopa, since L-dopa continued to induce circling behavior in animals with unilateral nigrostriatal lesions, even when these lesions approached totality.
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PMID:The site of dopamine formation in rat striatum after L-dopa administration. 720 52