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)

Expression of the dopaminergic phenotype in olfactory bulb (OB) juxtaglomerular neurons (constituting a population of periglomerular and external tufted cells) is dependent upon functional innervation by peripheral olfactory receptors. Loss of functional input in rodents, by either peripheral deafferentation or deprivation of odorant access, results in a profound decrease in the expression of juxtaglomerular tyrosine hydroxylase (TH). We have examined the effects of such treatments on the expression of the neurotransmitter biosynthetic enzyme glutamic acid decarboxylase (GAD), which is colocalized with TH in the majority of TH-containing juxtaglomerular neurons. Following either chemically induced OB deafferentation in adult mice or unilateral odor deprivation in neonatal rats, steady-state OB GAD messenger RNA levels remained essentially unchanged as assessed by Northern blot analysis 20-40 days after treatment. These results were confirmed by in situ hybridization analysis, which demonstrated a profound loss of juxtaglomerular TH messenger RNA but no accompanying decrease in regionally colocalized GAD message. Since GAD is found in nearly all dopaminergic OB cells, the preservation of juxtaglomerular GAD message implies that olfactory receptor neurons exert a differential transneuronal regulation of TH and GAD gene transcription.
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PMID:Differential effect of functional olfactory bulb deafferentation on tyrosine hydroxylase and glutamic acid decarboxylase messenger RNA levels in rodent juxtaglomerular neurons. 168 68

We describe a new method that can determine transmitter phenotype of proliferating nerve cells at a given age. The procedure is based on indirect sequential double antigen immunofluorescence histochemistry for transmitter-synthesizing enzymes (glutamic acid decarboxylase and tyrosine hydroxylase) and the thymidine analogue, bromodeoxyuridine. The method permits simple, rapid, and effective anatomical detection, and promises to reduce certain limitations inherent in a combination with tritiated thymidine autoradiography. Employing this technique, we observed that many striatal cells expressing gamma-aminobutyric acid (GABA) and nigral cells expressing dopamine undergo the final mitosis at embryonic days 13-14 in the rat.
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PMID:Double immunohistochemical detection of transmitter phenotype of proliferating cells using bromodeoxyuridine. 168 5

In mouse, rat, and monkey, N-methyl-D,L-aspartic acid (NMDA) modulates gonadotropin releasing hormone (GnRH) release by an unknown mechanism. In previous studies we found that normal male mice consistently responded to NMDA administration with increased levels of plasma LH, as did most normal female mice and female hypogonadal mice with fetal preoptic area implants (HPG/POA). To investigate the mechanism of NMDA-induced GnRH release, immunocytochemistry of c-fos protein (FOS) was used for detection of neurons activated by NMDA administration. In both normal male and HPG/POA mice, FOS expression was unchanged in GnRH cells after NMDA administration. That neurosecretory cells can respond to NMDA was shown by the induction of FOS in many CRH (corticotropin-releasing hormone) cells in the paraventricular nucleus. Immunocytochemistry of beta-Endorphin, neuropeptide Y, tyrosine hydroxylase, an enzyme marker for catecholaminergic neurons, and glutamic acid decarboxylase, an enzyme marker for GABA neurons, was combined with that for FOS in normal male mice. Many noradrenergic (NA) neurons in the locus coeruleus (32-61%), and dopaminergic (DA) neurons in the mediobasal hypothalamus (15-31%) expressed FOS after NMDA administration while FOS was only rarely induced in neurons with the other neuromodulators tested. FOS was also induced in the locus coeruleus in male (43, 54%) and female (40, 55, 69%) HPG/POA mice. In contrast, few cells of the locus coeruleus expressed FOS in normal or HPG/POA mice after saline challenge. These results suggested that NMDA did not activate GnRH cells directly, but that NA neurons in the locus coeruleus were activated by NMDA and might be involved in stimulating GnRH release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Norepinephrine neurons in mouse locus coeruleus express c-fos protein after N-methyl-D,L-aspartic acid (NMDA) treatment: relation to LH release. 168 42

A comparative analysis of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity in the olfactory bulb was conducted in the hamster and rat. The distribution and morphological features of NADPH-stained neurons were compared to those of glutamic acid decarboxylase-like (GAD-LI) and tyrosine hydroxylase-like (TH-LI) immunoreactive somata in order to relate NADPH-staining to neuronal classes with specific biochemical properties. Intense NADPH-staining was located in primary nerve fibers of the accessory and main olfactory systems, producing dense staining of individual glomeruli. The entire vomeronasal nerve and all glomeruli were stained in the accessory olfactory bulb, but olfactory nerve and glomerular staining were restricted to the dorsal half of the main olfactory bulb. The glomerular layer of the main olfactory bulb of both animals contained numerous small NADPH-stained neurons. The range of somal areas of these neurons was relatively narrow and averaged about 60 microns2 (ca. 8 x 11 microns). Most neurons possessed ovoid somata and monoglomerular intraglomerular dendrites. Previous Golgi studies indicate that such features characterize periglomerular cells. The somal areas of GAD-LI somata in the glomerular layer overlapped that of the NADPH-stained neurons, providing additional evidence that these neurons are probably periglomerular cells. The range of somal areas of TH-LI somata in the glomerular layer was broader and included both small and large neurons that usually possessed intraglomerular dendritic tufts. The smaller TH-LI somata corresponded in size to both the NADPH-stained and GAD-LI somata, suggesting an interrelationship among periglomerular cells, GAD-LI, TH-LI, and NADPH-diaphorase activity. The larger TH-LI somata were probably external tufted cells. In the external plexiform layer of the hamster, oriented NADPH-stained neurons were observed that possessed an intraglomerular dendrite. These neurons appeared to be middle tufted cells. Lightly stained and smaller neurons were occasionally seen in the mitral body and internal plexiform layers, corresponding in somal area and morphological features to those of type III granule cells. No internal tufted or mitral cells were stained. The largest NADPH-stained neurons were located in the inner half of the granule cell layer and were classified as Golgi cells. Their somata averaged 125 microns2 (ca. 10 x 17 microns). Many NADPH-stained neurons were observed in all subdivisions of the anterior olfactory nucleus, the anterior hippocampal rudiment, anterior and posterior levels of the piriform cortex, and the vertical and horizontal limbs of the diagonal band of Broca, all of which are known to provide centrifugal inputs to the olfactory bulb.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:NADPH-diaphorase activity in the olfactory system of the hamster and rat. 168 89

The lateral geniculate complex (GL) of pigeons was investigated with respect to its immunohistochemical characteristics, retinal afferents, and the putative transmitters/modulators of its neurons. The distributions of serotonin-, choline acetyltransferase-, glutamic acid decarboxylase-, tyrosine hydroxylase-, neuropeptide Y- (NPY), substance P- (SP), neurotensin- (NT), cholecystokinin- (CCK), and leucine-enkephalin- (L-ENK) like immunoreactive perikarya and fibers were mapped. Retinal projections were studied following injections of Rhodamine-B-isothiocyanate into the vitreous. Transmitter-specific projections onto the visual Wulst and the optic tectum were studied by simultaneous double-labelling of retrograde tracer molecules and immunocytochemical labelling. The GL can be divided into three major subdivisions, the n. geniculatus lateralis, pars dorsalis (GLd; previously designated as the n. opticus principalis thalami, OPT), the n. marginalis tractus optici (nMOT), and the n. geniculatus lateralis, pars ventralis (GLv). All three subdivisions are retinorecipient. The GLd can be further subdivided into at least five components differing in their immunohistochemical characteristics: n. lateralis anterior (LA); n. dorsolateralis anterior thalami, pars lateralis (DLL), n. dorsolateralis anterior thalami, pars magnocellularis (DLAmc); n. lateralis dorsalis nuclei optici principalis thalami (LdOPT); and n. suprarotundus (SpRt). The LdOPT consists of an area of dense CCK-like and NT-like terminals of probable retinal origin. Three subnuclei (DLL, DLAmc, SpRt) were shown to project to the visual Wulst. Cholinergic and cholecystokinergic relay neurons participated in this projection. The nMOT occupies a position between the GLd and GLv and encircles the rostral pole of n. rotundus and the LA. It is characterized mainly by medium sized NPY-like perikarya which were shown to project onto the ipsilateral optic tectum. Bands of NPY-like fibers in the tectal layers 2, 4, and 7 could at least in part be due to this projection of the nMOT. Most of the antisera used revealed transmitter/modulator-specific fiber systems in the GLv which often showed a layer-specific distribution. Perikaryal labelling was only obtained with glutamic acid decarboxylase. On the basis of its chemoarchitectonics, topography, and connectional pattern, the GLd complex of pigeons is most directly equivalent to the mammalian GLd. However, although the different subdivisions of the avian GLd may represent functionally different channels within the thalamofugal pathway similar to the lamina-specific differentiation within the mammalian geniculostriate projection, direct comparison of subnuclei of birds and mammals is not justified at this time. The nMOT appears similar to the intergeniculate leaflet (IGL) and the avian GLv clearly corresponds in many features to the mammalian GLv.
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PMID:An immunocytochemical analysis of the lateral geniculate complex in the pigeon (Columba livia). 168 43

The striatonigral pathway contains several neurotransmitters which may regulate the activity of the nigrostriatal dopamine projection in the rat. This was investigated by measuring extracellular dopamine levels in the striatum, using microdialysis, after injections of GABA (300 nmol/0.2 microliters), dynorphin A (0.5 nmol/0.2 microliters), substance P (0.07 mnol/0.2 microliters) or neurokinin A (0.09 nmol/0.2 microliters) into the ipsilateral substantia nigra, pars reticulata (SNR). Intranigral injections of GABA or dynorphin A inhibited, while intranigral injections of substance P or neurokinin A stimulated dopamine levels in the ipsilateral striatum. In rats with ibotenic acid lesions (2.5 micrograms/0.5 microliters) in the SNR, intranigral injections of GABA or dynorphin A inhibited, while intranigral injections of substance P or neurokinin A stimulated dopamine levels in the ipsilateral striatum. These responses were not significantly different than those in unlesioned rats. Analysis of the intranigral lesion with in situ hybridization revealed a heavy loss of glutamic acid decarboxylase mRNA expression in the SNR and a significant loss of tyrosine hydroxylase (TH) mRNA expression in the SNC. Immunohistochemical analysis revealed a disappearance of TH-Like immunoreactivity (LI) im dendrites in the SNR, a considerable loss of TH-LI cell bodies in the SNC and a restricted loss of neuropeptide K-LI in the SNR around the tip of the injection cannula. Furthermore, lesioned rats rotated ipsilateral to the lesion after apomorphine (1 mg/kg, s.c.), indicating that the basal ganglia output mediated via the SNR GABA neurons was impaired on the lesioned side. Analysis of the striatum revealed that a dense TH-LI fiber network could still be seen on the lesioned side. Furthermore, basal and amphetamine stimulated extracellular dopamine levels in the striatum on the lesioned side were not significantly depleted. This indicates that the ascending nigrostriatal dopamine projection was functionally intact on the lesioned side. These findings indicate that intranigral GABA, dynorphin A, substance P and neurokinin A modulation of ipsilateral striatal dopamine release is mediated via direct action on the nigrostriatal projection. Thus, it is suggested that the striatonigral pathway, which contains GABA, dynorphin, substance P and neurokinin A, exerts a direct regulatory effect on the activity of the nigrostriatal dopamine projection.
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PMID:Striatonigral GABA, dynorphin, substance P and neurokinin A modulation of nigrostriatal dopamine release: evidence for direct regulatory mechanisms. 170 47

The axonal transport blocker colchicine has been extensively used in immunohistochemical studies to induce accumulation of neuroactive compounds, especially neuropeptides, in neuronal somata and thus improve their visualization. To assess whether colchicine might, in addition, influence the synthesis of such compounds, we have now used in situ hybridization to examine the levels of mRNAs encoding for several neuropeptides (galanin [GAL], cholecystokinin [CCK], somatostatin [SOM], neuropeptide Y [NPY]) and neurotransmitter-synthesizing enzymes (choline acetyltransferase [ChAT], tyrosine hydroxylase [TH], amino acid decarboxylase [AADC], and glutamic acid decarboxylase [GAD]) after intraventricular administration of the drug. The results show that colchicine differentially modifies the levels of several mRNA species in different brain areas. Thus GAL mRNA levels increase in virtually all regions examined, including the basal forebrain, hypothalamus, dorsal raphe nucleus, locus coeruleus, and nucleus tractus solitarii. In addition, after colchicine treatment, GAL mRNA appears to be induced in the ipsilateral hemisphere in regions such as the cortex, hippocampus, striatum, lateral septum, and some nuclei of the thalamus as well as within white matter, where it cannot be detected in control animals. Although GAL mRNA in the vast majority of cases is neuronal, some findings indicate a possible glial localization. In parallel, colchicine depletes ChAT mRNA and increases GAD mRNA in the basal forebrain and striatum and decreases AADC mRNA in the dorsal raphe nucleus and locus coeruleus. In the latter nucleus, NPY and TH mRNA levels are increased by colchicine. In contrast, TH mRNA and also CCK mRNA levels decrease in the substantia nigra. In the cortex, hippocampus, and thalamus ipsilateral to colchicine injection CCK mRNA levels are markedly decreased, whereas SOM mRNA is decreased and NPY mRNA increased in the hippocampus but unchanged in the cortex. The results are discussed with reference to the possible artifacts that the use of colchicine might induce in immunohistochemical mapping studies and in relation to possible neurotoxic actions of colchicine, in some cases perhaps related to impaired retrograde transport of growth factor(s).
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PMID:Differential effects of intracerebroventricular colchicine administration on the expression of mRNAs for neuropeptides and neurotransmitter enzymes, with special emphasis on galanin: an in situ hybridization study. 170 58

Rat E15 retina was grafted to the retina of adult rat hosts. After varying survival times (1 week-6 months), grafts were stained by immunohistochemistry for neurofilament 160 kDa (NF), HPC-1 (an amacrine cell marker), choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD) and somatostatin-28 (SS-28). The first differentiating graft amacrine cells (cholinergic and dopaminergic) could be seen 1 week after transplantation (corresponding to postnatal day 1 = P1). The inner plexiform layer of the graft started to differentiate at 2 weeks (corresponding to P8) seen by HPC-1 and GAD staining. ChAT, TH and SS-28 immunostaining revealed an abnormal lamination pattern in the graft inner plexiform layer. Also by 2 weeks, the outer plexiform layers of the graft contained NF-immunoreactive horizontal cells. No NF-stained retinal ganglion cells could be observed in the graft. Five and 7 weeks after grafting, the transplants had obtained the same staining intensity with different markers as the host retina.
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PMID:Neuronal markers in rat retinal grafts. 197 41

We have used light-microscopical immunohistochemistry to investigate developmental changes of several neurochemical indicators in retinas of perinatal killifish and goldfish. Immunoreactive proliferating cell nuclear antigen (ir-PCNA/cyclin, a marker for replicating cells) was present in nuclei of all neuroblasts in the early monolayer stage, but was lost progressively in central-to-peripheral and proximal-to-distal order as the layers and cells of the mature retina appeared. The loss of ir-PCNA was slightly prior to the appearance of ir-TH (tyrosine hydroxylase), GAD (glutamic acid decarboxylase) and GS (glutamine synthetase) at the 4th embryonic day (E4) in both fish. Since hatching was earlier in goldfish (E5) than in killifish (E7), neurochemical maturation was evident at 2-3 days before hatching in killifish but not until around hatching in goldfish. Two markers, ir-somatostatin and protein kinase C, were detected by the 1st postnatal day (H1) in goldfish, but not in perinatal or adult killifish retinas. Thus the course of development of killifish and goldfish retinas is similar, but not identical. The validity of ir-PCNA as a marker for proliferating cells is confirmed by the coincidence of its disappearance with the appearance of neurochemical markers for mature, postmitotic retinal cells.
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PMID:Emergence and development of immunoreactive cells in teleostean retinas during the perinatal period. 197 54

The avian wulst, a laminated "bulge" in the dorsal telencephalon, contains several distinct regions. The posterolateral portion (visual wulst) has been proposed to be an avian equivalent of the mammalian striate cortex. The present study examines specific neurotransmitters and neuropeptides within the visual wulst by immunohistochemical techniques. Antisera and monoclonal antibodies against choline acetyltransferase (ChAT), nicotinic acetylcholine receptor (nAChR), tyrosine hydroxylase (TH), serotonin (5-HT), glutamic acid decarboxylase (GAD), gamma-aminobutyric acid A receptor (GABAAR), cholecystokinin (CCK), substance P (SP), leucine-enkephalin (L-ENK), neurotensin (NT), neuropeptide Y (NPY), somatostatin (SRIF), corticotropin-releasing factor (CRF), and vasoactive intestinal polypeptide (VIP) were used. Somata and neuropil displaying specific immunoreactivity were generally distributed in accordance with the laminar cytoarchitectonic organization of the wulst. The superficial layer of the wulst, the hyperstriatum accessorium, contained the highest densities of TH-, 5-HT-, SP-, NPY-, SRIF-, CRF-, and VIP-positive neuropil in the wulst, whereas the highest density of CCK- and NT-staining was found in the deepest layer of the wulst, the hyperstriatum dorsale. In addition to the traditionally defined four laminae of the wulst, the immunoreactive staining revealed several subregions within each lamina. The most dorsolateral portion of the wulst contained the highest densities of ChAT- and L-ENK-stained fibers in the wulst, as well as moderately dense staining of neuropil for 5-HT-, TH-, SP-, and CCK-like immunoreactivity. The nAChR-immunoreactivity was faint and distributed rather uniformly throughout the wulst. The results suggest that the wulst consists of multiple regional variations within layers comparable to laminar variations found within different cytoarchitectonic areas of the mammalian neocortex.
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PMID:Immunohistochemical analysis of the visual wulst of the pigeon (Columba livia). 197 83


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