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

A unilateral administration of 6-hydroxydopamine into the nigrostriatal system of the rat was responsible for ipsiversive circling behaviour in response to administration and, in time, of contraversive circling behaviour in response to L-DOPA and apomorphine. This contraversive circling behaviour appears to be mediated by the development, on the lesioned side, of supersensitivity of postsynaptic dopamine receptors. Subchronic treatment with cytidine-5'-diphosphocholine (p.o.) by itself was devoid of behavioural effects. The CDP-choline did not modify the apomorphine-induced stimulant effect but potentiated the circling behaviour produced by L-DOPA and amphetamine. The data show that the effects of CDP-choline were mediated by a presynaptic mechanism: the potentiation of the effects of L-DOPA cannot be explained by an activation of tyrosine hydroxylase, but seems to be related to an improvement of release of newly synthesized dopamine from exogenous L-DOPA.
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PMID:Circling behaviour in rats with unilateral lesions of the nigrostriatum induced by 6-hydroxydopamine: changes induced by oral administration of cytidine-5'-diphosphocholine. 311 33

The mechanisms underlying the response of the brain to ischemia are not fully understood. Biochemical and morphological changes following neocortical infarction can be investigated in rats using a model of focal cerebral ischemia induced by unilateral occlusion of the middle cerebral artery (MCA). Evaluation of ischemic damage often employs conventional histologic stains. Immunocytochemistry can be used as a valuable tool in this model to define changes in specific proteins of interest. In this study, an antiserum raised against insulin-like growth factor II (IGF-II) receptor was used to evaluate changes of IGF-II receptor immunoreactivity in the cerebral cortex of rats 4 and 7 days following permanent MCA occlusion. IGF-II receptor immunoreactivity was found to be associated with neocortical pyramidal neurons within the core of the ischemic infarct itself. The staining intensity was markedly elevated above that observed in nonischemic neurons. Immunopositive neurons exhibited a punctate staining pattern. These neurons appeared to correspond to argentophilic neurons, as defined by modified Bielschowsky silver staining. Evaluation of other neuronal markers revealed the absence of immunoreactivity for neuron-specific enolase and for tyrosine hydroxylase within the ischemic area. These observations show an increase in a specific growth factor receptor within neurons in the ischemic core of a focal infarct several days following permanent focal infarction, a time when neurons are presumed to be dead. The significance and the potential role of IGF-II receptor in lesion-induced plasticity are discussed.
J Cereb Blood Flow Metab 1995 Nov
PMID:Increase in insulin-like growth factor II receptor within ischemic neurons following focal cerebral infarction. 759 34

Dopamine has been implicated in the pathophysiology of schizophrenia, and the entorhinal cortex (ERC) is thought to be a site of structural pathology in this disorder. However, relatively little is known about the dopaminergic (DA) innervation of ERC in the primate brain. In this study, immunohistochemical methods and antibodies directed against tyrosine hydroxylase (TH) and dopamine were used to determine the organization of DA axons in the ERC of macaque monkeys. The anti-TH antibody used in this study appeared predominantly to identify DA axons, as demonstrated by its failure to label fibers that were immunoreactive with an antibody against dopamine-beta-hydroxylase in double-labeling experiments. In addition, the regional and laminar distributions of TH-immunoreactive fibers were strikingly similar to those labeled with the anti-dopamine antibody. With both antibodies, cytoarchitectonically identified subdivisions of monkey ERC (Amaral et al., 1987) differed in both the density and laminar distribution of labeled fibers. Immunoreactive processes exhibited a substantial rostral-to-caudal gradient of decreasing density across subdivisions of ERC, and the density of labeled fibers also decreased from medial to lateral in the rostral but not in the caudal subdivisions of ERC. The laminar distribution of labeled fibers differed both between and within subdivisions. For example, in the olfactory and rostral subdivisions of ERC, the superficial layers contained a very high density of immunoreactive processes, whereas in the intermediate region, three bands of labeled fibers were seen in layers I, III-IV, and VI. In addition, radial columns of fibers interdigitated with areas of decreased density were present between layers I and III. Although the overall density of labeled fibers was greater in lateral than in the caudal subdivisions of ERC, these regions had similar laminar distribution patterns. In these areas of monkey ERC, labeled processes were highest in density in deep layer I, and homogeneously distributed in the other cortical layers. These findings demonstrate that the DA innervation of monkey ERC is complex, and follows laminar- and subdivision-specific patterns. These patterns of distribution suggest the possible interactions that DA axons may have with other elements of ERC circuitry, and may provide insight into the possible functional roles of dopamine in ERC in both normal and disease states.
Cereb Cortex
PMID:The dopaminergic innervation of monkey entorhinal cortex. 790 2

The mesencephalic dopaminergic system has been implicated in the motor and cognitive operations of the cerebral cortex as well as in the pathogenesis of neurological and psychiatric disorders. However, to date, the dopamine (DA)-containing axons of the primate cerebral cortex have not been directly visualized immunohistochemically due to the lack of a DA-specific antibody. We have now analyzed the regional and laminar distribution of DA-immunoreactive (DA-IR) afferents in the frontal cortex of the rhesus monkey using a monoclonal antibody specific for DA. In addition, we compared the distribution of DA-IR processes to tyrosine hydroxylase (the rate-limiting enzyme in DA synthesis) immunoreactive (TH-IR) axons. Frontal cortex displays an elaborate and robust dopaminergic innervation. Although regional differences in the DA-IR innervation were clearly evident, variations in the DA innervation were essentially unrelated to cytoarchitectonic boundaries. Instead, the DA innervation followed two basic gradients: (1) a prominent medial-to-lateral gradient of decreasing fiber density that was most prominent in the dorsal cortical regions, and (2) a more subtle anterior-posterior gradient in which DA-IR fiber density decreased slightly in both rostral and caudal directions from a peak density centered in the region of granular frontal area 8Bm and the supplementary motor area 6M. The laminar pattern of DA-IR axons also showed regional variations that again were typified by smooth transitions irrespective of cytoarchitecture. Analysis of DA-IR axonal morphology indicated that immunoreactive fibers form a basically uniform population, giving little evidence of a bimodal heterogeneity evident in other species.(ABSTRACT TRUNCATED AT 250 WORDS)
Cereb Cortex
PMID:Characterization of the dopaminergic innervation of the primate frontal cortex using a dopamine-specific antibody. 810 Jul 25

In the present study the topographical distribution of the intrinsic nerve plexuses of the basal cerebral arteries in humans was quantified and the relation between vessel diameter and nerve density was investigated. Whole-mount preparations of various segments of the basal cerebral arteries from middle-aged patients were stained for protein gene product (PGP) 9.5. The deep nerve plexuses, located at the adventitial-medial border, were quantified by image analysis. Confocal scanning laser microscopy was used to study nerve plexuses throughout the adventitia. Transverse cryostat sections were stained for PGP 9.5, tyrosine hydroxylase and neurofilament, and quantified. The results showed a three-layered configuration of the adventitial nerves. Measurements on whole-mounts demonstrated that nerve densities were highest in the posterior communicating artery (PCom), and next highest in the proximal parts of the posterior cerebral artery (PCA) and anterior choroidal artery. There appeared to be no clear relation between nerve density and vessel diameter. The measurements on sections confirmed the high nerve densities in the PCom and PCA. Tyrosine hydroxylase- and neurofilament-immunoreactivities appeared to demonstrate separate subpopulations of the overall nerve plexuses, representing sympathetic and, possibly, sensory fibers, respectively. Densities of both subgroups generally followed those of PGP 9.5-immunoreactive nerves. Transmission electron microscopy suggested motor function of the deep nerve plexuses. The results indicate a stronger neuronal influence on this part of the cerebral circulation than hitherto reported. It is concluded that human basal cerebral arteries display a topographical distribution of deep perivascular nerves, and that nerve density is determined by locality rather than by vascular diameter.
J Cereb Blood Flow Metab 1996 Sep
PMID:Perivascular nerves of the human basal cerebral arteries: I. Topographical distribution. 878 49

Tyrosine hydroxylase of catecholamine neurons catalyzes the synthesis of 3,4-dihydroxphenylalanine (DOPA), which is subsequently metabolized to dopamine by DOPA decarboxylase (DDC). However, DOPA is not committed to decarboxylation in vivo because export of DOPA from brain and metabolism of DOPA other than decarboxylation are possible. To estimate the relative magnitudes of the several fates of DOPA, the kinetics of the uptake and metabolism of L-[3H]tyrosine ([3H]Tyr, intravenous infusion) was measured in brain of rats pretreated with NSD 1015, an inhibitor of DDC. Some rats were pretreated with haloperidol before the blockade of DDC. The [3H]Tyr was incorporated into brain protein at a rate constant of 0.03 min(-1). The relative tyrosine hydroxylase activity in striatum was 0.005 min(-1) at 30 minutes after NSD 1015, 0.011 min(-1) 3 hours later, and 0.020 min(-1) after haloperidol treatment. The rate constant for the clearance of DOPA from brain (0.06 min(-1)) and earlier estimates of the rate constant of DDC activity in striatum (0.26 min(-1)) together predict that 80% of DOPA formed in normal rat striatum normally is available for dopamine synthesis. It follows that modulation of DDC activity can influence the rate of DA synthesis by affecting the relative magnitude of the several fates of DOPA in living brain.
J Cereb Blood Flow Metab 1998 May
PMID:[3H]DOPA formed from [3H]tyrosine in living rat brain is not committed to dopamine synthesis. 959 41

The dopaminergic innervation of the frontal cortex, commonly implicated in psychiatric and neurological disorders, has traditionally been associated with a circumscribed midline group of ventral tegmental area (VTA) neurons. We have employed a combination of retrograde tracing, using fluorescent dyes, and tyrosine hydroxylase (TH) immunohistochemistry to amplify knowledge of frontal cortex-projecting dopamine (DA) neurons in non-human primates. Injections of retrograde fluorochromes were made in areas 46, 8B/6M, 12, 4, 24, and the prelimbic (PL) and infralimbic areas (IL) of the rhesus monkey. The mesencephalic distribution of neurons exhibiting both retrograde labeling and TH immunoreactivity or retrograde labeling alone was examined from the level of the mammillary bodies to the locus coeruleus. DA afferents innervating the macaque frontal cortex as a whole originate from an unexpectedly widespread continuum of neurons distributed in the dorsal aspects of all three of the mesencephalic DA cell groups [A9, A10 and A8; generally corresponding to the DA cells of the substantia nigra (SN), VTA, and the retrorubral area (RRA) respectively]. A large number of these retrogradely labeled neurons are non-dopaminergic. The dorsal frontal cortex (areas 46, BB/6M and 4) receive DA projections primarily from the full medial-lateral extent of A9 cells dorsal to the SN pars compacta (i.e. A9 dorsalis), the RRA and to a lesser extent from the A10 parabrachial pigmented nucleus (PBPG) and linear nuclei, the latter of which have been associated with the mesocortical DA system. In contrast, the ventromedial PL and IL exhibit a significantly more robust input from the PBPG and midline linear VTA nuclei than from the lateral groups. The anterior cingulate cortex (area 24) is innervated by a group of DA neurons primarily located between these laterally and medially concentrated populations. These findings demonstrate a degree of compartmentalization of the mesofrontal DA system in primates, and suggest that this projection should no longer be viewed as a unitary midline system.
Cereb Cortex 1998 Jun
PMID:Widespread origin of the primate mesofrontal dopamine system. 965 Nov 29

Dopamine afferents from the mesencephalon appear to play a critical role in the normal development and cognitive functions of multiple areas of the primate cerebral cortex. In some regions, such as the prefrontal and motor cortices, dopamine innervation changes substantially during postnatal development. However, little is known about the postnatal maturation of dopamine afferents to the primate rostral entorhinal cortex, a periallocortical region that receives a dense dopamine innervation in adults. In this study, we used immunocytochemical techniques and antibodies against tyrosine hydroxylase and the dopamine transporter to examine the postnatal development of dopamine axons in the rostral subdivision of macaque monkey entorhinal cortex. Within animals, the axons labeled with each antibody did not differ in overall density or laminar distribution. Across development, the density of dopamine axons in layers I and VI did not change appreciably. In contrast, the density of labeled axons in layer III significantly increased by a factor of three between birth and 5-7 months of age. The timing of this change differs substantially from that observed in prefrontal cortex, where peak dopamine innervation occurs between 2 and 3 years of age. These findings, in concert with other data, suggest that developmental changes in the dopamine innervation of cortical regions may parallel the functional maturation of those areas.
Cereb Cortex
PMID:Postnatal development of tyrosine hydroxylase- and dopamine transporter-immunoreactive axons in monkey rostral entorhinal cortex. 972 85

The ability of dopamine to regulate the cognitive functions of the prefrontal cortex (PFC) involves complex modulatory actions on GABA-containing local circuit neurons in addition to pyramidal cells. However, the subclasses of cortical neurons that receive direct dopamine input are not known. We sought to determine whether dopamine terminals innervate the subclasses of local circuit neurons that contain the calcium-binding protein parvalbumin (PV), namely the wide arbor and chandelier neurons that target pyramidal cell soma and axon initial segments respectively. Sections through area 9 of five monkeys were labeled with immunoperoxidase for tyrosine hydroxylase (TH), to identify dopamine terminals, and with immunogold-silver for PV. Electron microscopic examination of the middle cortical layers (IIIb-IV) revealed that TH-positive terminals were sometimes directly apposed to PV-labeled dendrites, and approximately one-third of these contacts exhibited morphological features that are typically associated with symmetric synapses. In contrast, TH-immunolabeled terminals in the superficial layers (I-IIIa) were less frequently apposed to PV-positive dendrites, and none of these contacts exhibited synapse-like morphology. These findings, in concert with previous studies of GABA- or calretinin-containing local circuit neurons, suggest that dopamine's modulatory action in the PFC involves selective effects on only certain interneuron populations, including those that mediate potent inhibitory actions on pyramidal cells.
Cereb Cortex
PMID:Dopamine innervation of a subclass of local circuit neurons in monkey prefrontal cortex: ultrastructural analysis of tyrosine hydroxylase and parvalbumin immunoreactive structures. 982 82

Changes in gonadal hormones induced early in life produce substantial, seemingly permanent decreases in tyrosine hydroxylase (TH)-immunoreactive axon density in sensory, motor and prefrontal regions in the rat cerebral cortex. Less is known, however, about the responsiveness of cortical catecholamines to hormone stimulation during adulthood. In this study we expanded upon an earlier analysis of the effects of acute (4 day) and chronic (28 day) gonadectomy in adult male rats on TH innervation in right hemifield of the cingulate cortex to include assessment of sensorimotor areas previously examined following perinatal gonadectomy, the left cingulate hemifield, and one additional prefrontal area - the dorsal anterior insular cortex. Qualitative and quantitative analyses of immunoreactivity revealed modest, transient declines in innervation in sensorimotor areas 4 days after gonadectomy, and a return to normal innervation densities by 28 days after surgery. In cingulate and insular cortices, however, strikingly depleted axon densities observed following acute gonadectomy rebounded to significantly higher than normal levels of innervation 3 weeks later. All effects were attenuated in gonadectomized animals supplemented with testosterone. Thus, for cortical catecholamine innervation, as for other endpoints of hormone stimulation, gonadal steroid sensitivity appears to change dramatically with lifestage. In adult male rats, this sensitivity is also marked by a seemingly selective vulnerability of catecholamine innervation in prefrontal areas to changes in the hormone environment induced by gonadectomy.
Cereb Cortex
PMID:Regionally selective effects of gonadectomy on cortical catecholamine innervation in adult male rats are most disruptive to afferents in prefrontal cortex. 1045 Aug 95


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