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 neurotrophin brain-derived neurotrophic factor (BDNF) was tested for its ability to promote the survival and regulation of expression of phenotypic markers of dopaminergic, serotonergic, and GABAergic neurons in free-floating roller tube cultures of human fetal ventral mesencephalon. This culture system contains neurons of the anlage of the substantia nigra as well as that of the rostral raphe nucleus. Dopaminergic neuron number and tyrosine hydroxylase (TH) fiber density was monitored by TH immunocytochemistry. Measurement of dopamine (DA) content, TH enzymatic activity, serotonin (5-HT) content, and glutamic acid decarboxylase (GAD) activity were used as indices of their respective neurotransmitter function. The presence of GABAergic and serotonergic neurons in this culture system was confirmed by GABA and 5-HT immunocytochemistry. In cultures maintained in the presence of BDNF (10 ng/ml), the density of TH-positive cells was increased by 2.5-fold (P F 0.05), and the TH-positive fiber density was increased by 3.5-fold (P F 0.01), relative to control cultures. Similarly, the relative increases in DA content and TH activity were 2.6- and 2.3-fold, respectively, in the BDNF-treated cultures (P F 0.01 and P F 0.01). On a per neuron basis, DA content and TH activity were not markedly changed by BDNF treatment, suggesting that the increases in DA content and TH activity are due to more DA neurons surviving. Relative elevations were also observed in serotonin content (2.0-fold, P F 0.01) and GAD enzymatic activity (1.4-fold, P F 0.01). Future studies will need to determine whether these changes result from the direct action of BDNF on these neurons or through some indirect mechanism. The results demonstrate that BDNF has beneficial effects on cultured human fetal tissue, which may be relevant in optimizing neuronal transplantation techniques, and that multiple systems are simultaneously influenced by BDNF.
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PMID:Effects of BDNF on dopaminergic, serotonergic, and GABAergic neurons in cultures of human fetal ventral mesencephalon. 760 Dec 63

This paper reviews some of the research which was performed in my laboratory over the past several years on neurotransmitter regulation of LHRH neuronal function. Evidence is provided that LHRH neurons are relatively unresponsiveness to norepinephrine in their normal resting state (plasma LH levels are low) and one cause of this may be due to inhibitory influences exerted by local GABA interneurons. Also described is evidence that concomitant with preovulatory LH surges and increases in hypothalamic NE secretion there also is an increase in tyrosine hydroxylase mRNA levels and in activity within medullary A1 noradrenergic neurons. As well, following orchidectomy, A1 neuronal TH mRNA levels, hypothalamic NE secretion and plasma LH concentrations increase. Moreover, electrical stimuli which evoke hypothalamic NE secretion also elevate TH mRNA levels in A1 noradrenergic neurons. These observations indicate that increases in hypothalamic NE secretion are due to increases in A1 neuronal activity. We also examined the effects of excitatory stimuli such as NMDA and NE on LHRH/LH release and determined if such secretion is coupled to increases in LHRH mRNA. Both neurotransmitters increase LHRH mRNA levels and LH secretion. However, these two events are not coupled as morphine, which amplifies NE-induced LHRH/LH release, also blocks NE-induced increases in LHRH mRNA levels. Evidence is presented that this amplifying effect of morphine is due to a suppression of tuberinfundibular dopamine secretion thus allowing NE to evoke the release of LHRH from axon terminals in the median eminence.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurotransmitter regulation of luteinizing hormone-releasing hormone neuronal function. 772 17

The persistence of high levels of B-50 in the adult brain is generally assumed to characterize neuronal systems capable of undergoing some form of plasticity such as axonal sprouting and regeneration. Since adult hypothalamo-neurohypophysial neurons are known to rapidly regenerate after being transected, the present study was undertaken to determine if such a capacity for regeneration could be related to the expression of this protein. Adult rats were killed by intraaortic perfusion of fixative either without lesion or at different delays after a surgical transection of the hypophysial stalk. Electron microscopy and laser scanning confocal microscopy were used to examine the regenerating axons after single or double immunocytochemical labeling of vibratome sections for B-50 and for various neuronal markers characterizing different types of neurohypophysial axons. In intact neurohypophysis, B-50 immunostaining was frequently associated with fibers immunoreactive to GABA or to tyrosine hydroxylase, whereas it was not detected within peptidergic neurohypophysial axons. In the lesioned neurohypophysis, B-50 was again frequently localized within axonal fibers immunoreactive to tyrosine hydroxylase or GABA. On the other hand, B-50 immunostaining was never detected within the numerous vasopressinergic or oxytocinergic axonal sprouts that regenerate all along the median eminence proximal to the lesion. These data indicate that persistence of high levels of B-50 within the neurohypophysis of adult rats is a specific feature of catecholaminergic and/or GABA-ergic axons innervating this region and that, contrasting to other neuronal systems, B-50 is not involved in the remarkable capacity for regeneration exhibited by the vasopressinergic and oxytocinergic neurohypophysial axons.
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PMID:Immunolocalization of B-50 (GAP-43) in intact and lesioned neurohypophysis of adult rats. 789 16

Serotonin modulates a variety of neural processes, and is present in a subpopulation of neurons in the raphe nuclei. To study their electrophysiological properties, cells from the mesopontine raphe nuclei of the neonatal rat were dissociated and grown for up to 10 weeks in microcultures. Approximately one third of the neurons were identified as serotonergic based on the presence of serotonin immunoreactivity, tryptophan hydroxylase immunoreactivity, or a high affinity monoamine transporter. About 5% of cultured raphe neurons contained tyrosine hydroxylase immunoreactivity, while 25% contained GABA immunoreactivity. However, no neurons contained both serotonin and tyrosine hydroxylase staining, and less than 1% displayed both serotonin and GABA immunoreactivities. Cultured serotonergic neurons did not exhibit pacemaker firing in the presence of alpha 1 adrenergic receptor agonists such as phenylephrine or norepinephrine. Approximately one third were hyperpolarized by serotonin or the selective serotonin1A receptor agonist, (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin. Virtually all serotonergic neurons responded to application of glutamate, kainate, N-methyl-D-aspartate, GABA, and glycine. Depolarizing and hyperpolarizing synaptic potentials blocked by glutamate or GABAA receptor antagonists were frequently observed in both serotonergic and non-serotonergic raphe neurons. Slow inhibitory postsynaptic potentials were evoked by activating single presynaptic serotonergic neurons with a brief intracellular current pulse. The slow inhibitory synaptic potential had a mean latency to onset of 35 +/- 5 ms, a duration of 0.8-2.6 s, and was inhibited by the serotonin1A autoreceptor antagonists, (-)propranolol and spiperone. The rising and falling phases of the inhibitory potential could be fit by single exponential functions with mean time constants of 53 +/- 8 ms and 504 +/- 78 ms, respectively. Serotonin1A receptor-mediated autoinhibition was observed in microcultures containing a solitary serotonergic neuron, and thus constituted synaptic serotonin release, responsiveness, and re-uptake by a single vertebrate neuron. In summary, histochemical and electrophysiological evidence was obtained for catecholaminergic, GABAergic, and glutamatergic non-serotonergic raphe neurons in culture, many of which formed functional synaptic connections with neighboring cells. Additionally, cultured mesopontine serotonergic neurons expressed many of the cytochemical markers, neurotransmitter receptors, and synaptic functions observed in such cells in vivo, but the proportion of neurons sensitive to serotonergic and adrenergic agonists was significantly less than that reported in vivo. For the first time, the kinetics and pharmacology of serotonergic synaptic transmission by a single vertebrate serotonergic raphe neuron were determined, and found to resemble those observed after extracellular stimulation of populations of raphe neurons in slices and in vivo.
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PMID:Electrophysiological and histochemical properties of postnatal rat serotonergic neurons in dissociated cell culture. 789 77

The presence of antibodies recognizing specific epitopes of dopaminergic neurons in serum of patients suffering of Parkinson's Disease (PD) as well as their capability to induce neuronal damage was investigated utilizing serum-free dissociated mesencephalic-striatal co-cultures. High affinity dopamine (DA) and GABA uptakes were assessed as specific, functional markers of dopaminergic and GABAergic cell viability, respectively. Heat-inactivated serum samples from 18 and 13 patients suffering from idiopathic and vascular parkinsonism, respectively and from 18 neurologic controls, were added to co-cultures on day 4 in vitro. Twenty four hours later, reconstituted rabbit complement was added for 60 min and uptake parameters as well as immunocytochemical staining for tyrosine hydroxylase (TH)-containing cells were subsequently assessed. DA, but not GABA, uptake was significantly decreased only when complement was added to cultures containing serum samples from 14 out of 18 patients with idiopathic parkinsonism and 3 out of 13 patients with vascular parkinsonism (Fisher test, P < 0.01). Complement addition to cultures containing serum samples from seropositive parkinsonian patients significantly reduced immunocytochemical staining of TH-containing cells. Seropositive and seronegative patients did not differ in demographic and clinical features. These results suggest that a complement-dependent humoral immune response occurs mainly in idiopathic parkinsonian patients, but its clinical relevance remains to be established.
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PMID:Parkinsonian serum carries complement-dependent toxicity for rat mesencephalic dopaminergic neurons in culture. 790 31

Saccadic omnipause neurons (OPNs) are essential for the generation of saccadic eye movements. In primates OPNs are located near the midline within the nucleus raphe interpositus (rip). In the present study we used several different neuroanatomical methods to investigate the transmitters associated with OPNs in the monkey. Immunolabeling for the calcium-binding protein parvalbumin was employed to mark OPNs in the monkey and define the homologous cell group in cat and human. The use of antibodies against GABA, glycine (GLY), glutamate (GLU), serotonin (5-HT), and tyrosine hydroxylase revealed that the somata of OPNs are GLY immunoreactive, but they are devoid of GABA and 5-HT immunostaining. In situ hybridization with the GAD67 mRNA probe confirmed the negative GABA immunostaining of OPNs. 3H-GLY was injected into a projection field of OPNs, the rostral interstitial nucleus of the medial longitudinal fascicle (riMLF)--the vertical saccadic burst neuron area. This resulted in selective retrograde labeling of the OPNs in rip, while no labeling was found in the superior colliculus, which sends an excitatory projection to the riMLF. The somata and dendrites of putative burst neurons in the riMLF were contacted by numerous GLY-immunoreactive terminals. The quantitative analysis of immunoreactive terminal-like structures contacting OPNs revealed a strong input from GLY- and GABA-positive terminals on somata and dendrites, whereas GLU-positive puncta were mainly confined to the dendrites. Very few 5-HT and catecholaminergic terminals contacted OPN somata. Our findings suggest that OPNs use GLY as a neurotransmitter, and they receive numerous contacts from GABAergic, glycinergic, and glutaminergic afferents, and significantly fewer from monoaminergic inputs.
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PMID:Neurotransmitter profile of saccadic omnipause neurons in nucleus raphe interpositus. 790 56

Previous studies have shown that many of the tyrosine hydroxylase-immunoreactive (TH-IR) amacrine cells in the retina of mammals also show GABA-like immunoreactivity (GABA-IR). However such co-localization has yet to be demonstrated in the rabbit retina. In this study the proportion of TH-IR amacrine cells that show GABA-IR has been determined in the retina of the cat, rat and rabbit following fixation with 4% paraformaldehyde plus varying concentrations of glutaraldehyde. In the retina of the cat and rat, most of the TH-IR amacrine cells showed GABA-IR following fixation using low concentrations (0.01 or 0.1%) of glutaraldehyde. However in the rabbit retina very few of the TH-IR amacrine cells showed GABA-IR unless the glutaraldehyde concentration in the fixative was 0.5% or greater. The results suggest that the dopaminergic amacrine cells in the rabbit retina contain only very low levels of GABA, which are close to the detection limit of the antibody.
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PMID:Co-localization of GABA- and tyrosine hydroxylase-like immunoreactivities in amacrine cells of the rabbit retina. 790 84

Treatment of P19 embryonal carcinoma cells with retinoic acid induces their differentiation into a population of cells consisting of neurons and other cell types normally derived from neuroectoderm. We used immunohistological and histochemical techniques to identify some of the neurotransmitters in the P19-derived neurons. The majority of neurons contained GABA, glutamic acid decarboxylase, and GABA-transaminase. Neuropeptide Y and somatostatin were less frequently found and both were partially co-expressed with GABA and with one another. Smaller numbers of cells were positive for tyrosine hydroxylase, DOPA decarboxylase, serotonin, calcitonin gene-related peptide, galanin and substance P. The variety and proportions of cells with different transmitter types were reproducible from one experiment to the next and varied very little over 40 days in culture except for cells containing enkephalin, which were abundant only in mature cultures of 32 days or more. Synapses formed between neurons and some contained both small clear and large dense-core vesicles within the presynaptic bouton. Because GABA, neuropeptide Y and somatostatin are abundant in P19-derived neurons as well as in embryonic neurons in rostral regions of the mammalian CNS, we suggest that the developmental events occurring in P19 cell cultures closely resemble those of the embryonic neuroectoderm.
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PMID:Neurons derived from P19 embryonal carcinoma cells have varied morphologies and neurotransmitters. 791 Jun 70

We have established a primary neuronal culture of the embryonic day 14 rat, ventral mesencephalic region, centered on the A8, A9, and A10 dopaminergic nuclei (approximately 1.0 mm3 of tissue). At 16 hr after plating on a substrate of poly-D-lysine, in a serum-free or serum-supplemented growth medium, using a microisland culturing method, 95% of the cells stained positive for neuron-specific enolase, 20% for tyrosine hydroxylase, and < 5% for vimentin. When the growth medium was supplemented with 10% fetal calf serum, the percentage of tyrosine hydroxylase-positive neurons increased significantly (p < 0.05) at the 7th and 10th days in culture, compared with the percentage present at 16 hr after plating. When cultured in a serum-free growth medium, the percentage of tyrosine hydroxylase-positive neurons decreased to < 5% and to 0% by the 5th and 7th days, respectively, while the percentage of GABA-IR neurons increased. The addition of serum to the serum-free culture rescued dopaminergic neurons from death induced by serum deprivation. The effect of serum was dependent both on the time of addition after plating, and on the percentage added. When the cells were plated in a serum-free medium, on a confluent, type 1 astrocyte monolayer, prepared from the ventral mesencephalon of the embryonic day 16 rat, the survival of dopaminergic neurons increased significantly (p < 0.01) at DIV5, versus survival after plating on poly-D-lysine. Conditioned medium prepared from the same mesencephalic type 1 astrocyte monolayer also rescued dopaminergic neurons from death. The rescue mediated by the astrocyte monolayer or the conditioned medium was not inhibited by the mitotic inhibitor cytosine arabino furanoside (1.0 microM). Type 1 astrocyte monolayers and conditioned media prepared from the striatum and cerebral cortex of the embryonic day 16 rat had weaker trophic effects than those mediated by mesencephalic glia. We conclude that serum deprivation causes the selective death of dopaminergic neurons in a primary culture of the rat E14 ventral mesencephalon. Type 1 astrocytes or the conditioned medium from type 1 astrocytes can rescue dopaminergic neurons from death induced by serum deprivation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mesencephalic type 1 astrocytes rescue dopaminergic neurons from death induced by serum deprivation. 791 55

Ultrastructural immunocytochemical identification of transmitters in afferent terminals and targets of individual physiologically characterized neurons is essential for understanding the complex circuitry within the mammalian neocortex. For this type of analysis, we examined the utility of combining in vivo intracellular recording and biocytin injections with silver intensified 1 nm immunogold labeling of GABA and the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH). These transmitters are found to local neurons and afferents known to prominently modulate the activity of pyramidal neurons in the neocortex. Individual neurons were physiologically characterized and filled with biocytin in the frontal cortex of anesthetized rats. The brains were then preserved by vascular perfusion with aldehydes. Single vibratome sections through the recording site were reacted (1) for immunoperoxidase detection of biocytin and (2) for immunogold labeling of GABA or TH. Dually labeled sections were processed for light microscopy or embedded in plastic for electron microscopy. The dense peroxidase product for biocytin was detected in pyramidal neurons. These were located in superficial as well as deep cortical laminae, and were readily distinguished from immunogold silver labeling. GABA labeled terminals formed symmetric synapses with larger biocytin filled dendrites, whereas the TH labeled terminals contacted distal dendrites and spines. Peroxidase labeling for biocytin also was seen in a few axon terminals forming synapses with unlabeled and with GABA immunoreactive dendrites. These results suggest that single pyramidal neurons of the rat frontal cortex receive dual input from both GABA and catecholamine terminals. Additionally, this study demonstrates the usefulness of silver enhancement of 1 nm colloidal gold prior to plastic embedding for electron microscopic detection of neurotransmitters within afferents and targets of neurons physiologically characterized in vivo.
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PMID:Analysis of synaptic inputs and targets of physiologically characterized neurons in rat frontal cortex: combined in vivo intracellular recording and immunolabeling. 791 89


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