UNIPROT:P50583 - FACTA Search

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Query: UNIPROT:P50583 (asymmetrical)
12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mediorostral neostriatum/hyperstriatum ventrale and neostriatum dorsocaudale of the domestic chick are crucially involved in filial imprinting and are major targets of mesotelencephalic dopaminergic projections. To better understand the functional role of dopamine in these forebrain regions, the ultrastructure of dopamine terminals was studied by serial section electron microscopy using immunohistochemical labeling with antibodies to tyrosine hydroxylase and dopamine. At light as well as electron microscopic level, dopamine and tyrosine hydroxylase-immunoreactive fibers were present at moderate densities in the mediorostral neostriatum/hyperstriatum ventrale and high densities in the neostriatum dorsocaudale. The frequency of tyrosine hydroxylase-immunoreactive profiles per unit area was significantly higher in the neostriatum dorsocaudale than in the mediorostral neostriatum/hyperstriatum ventrale. In both regions, tyrosine hydroxylase-immunoreactive terminals were relatively small, with mean areas of 0.55 microm(2) in the mediorostral neostriatum/hyperstriatum ventrale and 0.48 microm(2) in the neostriatum dorsocaudale. The majority of tyrosine hydroxylase-immunoreactive synapses were symmetrical (83% in the mediorostral neostriatum/hyperstriatum ventrale, 75% in the neostriatum dorsocaudale) as opposed to asymmetrical (17 and 25%, respectively), but there were also tyrosine hydroxylase-immunoreactive terminals which lacked clear synaptic specializations. The preferred targets of the synaptic tyrosine hydroxylase-immunoreactive terminals were dendritic shafts (64% in the mediorostral neostriatum/hyperstriatum ventrale, 63% in the neostriatum dorsocaudale) and less frequently dendritic spines (17 and 23%, respectively) or perikarya (19 and 14%, respectively). In both forebrain regions, immunoreactive terminals were often found in close apposition to unstained terminals making asymmetrical synapses. In conclusion, these results indicate that the ultrastructural features of dopamine terminals in the avian telencephalon are very similar to those described in mammals and that dopamine may exert its effects primarily by modulating excitatory inputs.
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PMID:A quantitative immuno-electron microscopic study of dopamine terminals in forebrain regions of the domestic chick involved in filial imprinting. 1203 48

We previously reported that 1 month following unilateral loss (>95%) of striatal dopamine, there is an increase in striatal glutamate function as measured by in vivo microdialysis and quantitative immuno-gold electron microscopy, Neuroscience 88, 1-16). The goal of this study was to determine the effect of bilateral loss of striatal dopamine on striatal glutamate function following acute or subchronic administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57/B6J mice. Animals were administered either single injections (ip) of 30 mg/kg/day for 7 days (subchronically treated group) or 20 mg/kg x 4 doses every 2 h (acutely treated group) of the toxin or saline. One month following the first injection, there was a 44 and 65% loss in the relative density of tyrosine hydroxylase (TH) immunolabeling within the dorsolateral striatum in the subchronically and acutely MPTP-treated groups compared to the saline group, respectively. There was a decrease in the basal level of extracellular glutamate within the striatum in the subchronically MPTP-treated animals compared to an increase in the acutely treated group in relationship to the saline group. Ultrastructurally, only in the acutely MPTP-treated group was there a decrease in the density of glutamate immunolabeling within nerve terminals associated with an asymmetrical synaptic contact in the dorsolateral striatum compared to either the subchronic or saline groups. In addition, there was a decrease in the relative density of GluR-2/3 subunit immunolabeling within the dorsolateral striatum in the acute MPTP compared to the saline group. These data indicate that differences in striatal glutamate function appear to be associated with the dosing interval of MPTP administration and the variable loss of striatal TH immunolabeling.
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PMID:Acute and subchronic MPTP administration differentially affects striatal glutamate synaptic function. 1266 50

A unilateral lesion of the rat nigrostriatal pathway with 6-hydroxydopamine (6-OHDA) results in a decrease in the basal extracellular level of striatal glutamate, a nearly complete loss of tyrosine hydroxylase (TH) immunolabeling, an increase in the density of glutamate immunogold labeling within nerve terminals making an asymmetrical synaptic contact, and an increase in the number of apomorphine-induced contralateral rotations. [Meshul et al. (1999) Neuroscience 88:1-16; Meshul and Allen (2000) Synapse 36:129-142]. In Parkinson's disease, a lesion of either the subthalamic nucleus (STN) or the motor thalamic nucleus relieves the patient of some of the motor difficulties associated with this disorder. In this rodent model, either the STN or motor thalamic nucleus was electrolytically destroyed 2 months following a unilateral 6-OHDA lesions. Following a lesion of either the STN or motor thalamic nucleus in 6-OHDA-treated rats, there was a significant decrease (40-60%) in the number of apomorphine-induced contralateral rotations compared to the 6-OHDA group. There was a significant decrease (<30%) in the basal extracellular level of striatal glutamate in all of the experimental groups compared to the sham group. Following an STN and/or 6-OHDA lesion, the decrease in striatal extracellular levels was inversely associated with an increase in the density of nerve terminal glutamate immunolabeling. There was no change in nerve terminal glutamate immunogold labeling in either the motor thalamic or motor thalamic plus 6-OHDA lesion groups compared to the sham group. The decrease in the number of apomorphine-induced rotations was not due to an increase in TH immunolabeling (i.e., sprouting) within the denervated striatum. This suggests that alterations in striatal glutamate appear not to be directly involved in the STN or motor thalamic lesion-induced reduction in contralateral rotations.
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PMID:Lesion of subthalamic or motor thalamic nucleus in 6-hydroxydopamine-treated rats: effects on striatal glutamate and apomorphine-induced contralateral rotations. 1469 16

The present study was undertaken to explore involvement of nitric oxide (NO) in the experimental models of Parkinson's disease. Neurodegeneration was induced by unilateral injections of 6-hydroxydopamine (6-OHDA) or lipopolysaccharide (LPS) in the right striatum. Lesions were functionally evaluated by amphetamine-induced asymmetrical behaviour and by decrease in the tyrosine hydroxylase (TH) immunostaining. An induction in the expression of iNOS and augmentation in nitrite content was observed in both the models. The extent of increase in iNOS expression was, however, different but the elevation in the nitrite content was comparable in both the models. The increase in iNOS expression inversely correlated with the tyrosine hydroxylase (TH) immunolabeling. Animals pretreated with a NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), exhibited complete protection against amphetamine induced rotations in both the models. Thus, augmented NO availability subsequent to iNOS induction seems to play an important role in the initial phase of neurodegeneration.
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PMID:Involvement of nitric oxide in neurodegeneration: a study on the experimental models of Parkinson's disease. 1594 31

Excitotoxicity has been suggested to play a pivotal role in the pathogenesis of Parkinson disease (PD). As subthalamic nucleus (STN) neurons express glutamate and are overactivated in parkinsonism, it seems that in PD dopaminergic (DA) neurons are under the influence of abnormally high levels of glutamate and consequently might be more vulnerable to neurodegeneration. To determine the contribution of the overactivated STN-SN pathway to the progression of PD, we studied the effect of prior unilateral STN lesion on the toxicity induced by subsequent administration of 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine (MPTP) to non-human primates. In animals from group 1, kainic-induced lesion of the STN was performed prior to the administration of MPTP whereas in animals from group 2, STN lesion was caused after animals had been chronically treated with MPTP. The lesion of the STN elicited a contralateral hemiballism in animals from group 1, and they developed an asymmetrical parkinsonism after being exposed to MPTP. The STN lesion produced an improvement in the contralateral parkinsonism and mild choreic movements in animals from group 2. Cell counting of tyrosine hydroxylase immunoreactive (TH-ir) cells was performed by stereology and showed a similar loss of TH-ir cells (approximately 85%) in the ipsilateral and contralateral SN to the lesioned STN. These data indicate that the surgical removal of the excitatory drive from the STN to SN neurons does not protect dopaminergic neurons against a chronic and extended toxic effect of MPTP and do not support the assumption that STN blockade might delay the progression of PD.
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PMID:Does increased excitatory drive from the subthalamic nucleus contribute to dopaminergic neuronal death in Parkinson's disease? 1680 73

Dopaminergic (DA) inputs to the basolateral nuclear complex of the amygdala (BLC) are critical for several important functions, including reward-related learning, drug-stimulus learning, and fear conditioning. Despite the importance of the DA projection to the BLC, very little is known about which neuronal subpopulations are innervated. The present study utilized dual-labeling immunohistochemistry at the electron microscopic level to examine DA inputs to pyramidal cells in the anterior basolateral amygdalar nucleus (BLa) in the rat. DA axon terminals and BLa pyramidal cells were labeled using antibodies to tyrosine hydroxylase (TH) and calcium/calmodulin-dependent protein kinase II (CaMK), respectively. Serial section reconstructions of TH-positive (TH+) terminals were performed to determine the extent to which these axon terminals formed synapses versus non-synaptic appositions in the BLa. Our results demonstrate that at least 77% of TH+ terminals form synapses in the BLa, and that 90% of these synapses are with pyramidal cells. The distal dendritic compartment received the great majority of these synaptic contacts, with CaMK+ distal dendrites and spines receiving one-third and one-half, respectively, of all synaptic inputs to pyramidal cells. Many spines receiving innervation from TH+ terminals also received asymmetrical synaptic inputs from putative excitatory terminals. In addition, TH+ terminals often formed non-synaptic appositions with axon terminals, most of which were putatively excitatory in that they were CaMK+ and/or made asymmetrical synapses. Thus, using CaMK as a marker, the present study demonstrates that pyramidal cells, especially their distal dendritic compartments, are the primary targets of dopaminergic inputs to the basolateral amygdala.
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PMID:Dopaminergic innervation of pyramidal cells in the rat basolateral amygdala. 1883 10

The basolateral nuclear complex of the amygdala (BLC) receives robust sensory inputs from the rhinal cortices (RCx) that are important for the generation of emotional behavior. The BLC is also one of the main targets of the mesolimbic dopamine (DA) system. DA potentiates cortical sensory inputs to the BLC, which leads to an increase in the excitability of BLC pyramidal cells. These findings suggest that there may be convergence of RCx and DA inputs onto the dendrites of pyramidal cells in the BLC. In the present study we used dual-labeling immunohistochemistry and anterograde tract-tracing at the ultrastructural level to test this hypothesis in the rat brain. RCx axons were labeled by Phaseolus vulgaris leucoagglutinin (PHA-L) injections, whereas tyrosine hydroxylase (TH) was used as a marker for DA axons. The extent of convergence of these axons was analyzed in the posterior subdivision of the basolateral nucleus (BLp), which is densely innervated by both inputs. RCx synapses were asymmetrical and mainly contacted dendritic spines (86.4%) and dendritic shafts (12.1%). TH-positive (TH+) terminals also mainly formed synapses (symmetrical) and appositions with spines and shafts of dendrites. However, ultrastructural analysis found a very low percentage of RCx terminals converging with DA terminals onto unlabeled dendrites (9.4%) and axons (7.5 %), or exhibiting direct contacts with TH+ terminals (3.8%). These findings suggest that the association of specific behaviorally salient sensory stimuli with dopamine release in the BLC is not dependent on a point-to-point spatial relationship of cortical and DA inputs.
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PMID:Limited convergence of rhinal cortical and dopaminergic inputs in the rat basolateral amygdala: an ultrastructural analysis. 2034 51

Orexins are expressed in neurons of the dorsolateral hypothalamus and their axons widely distribute throughout the central nervous system. The noradrenergic cell groups of the lower brainstem belong to the targets of these orexin projections. Double immunostainings for orexin and phenylethanolamine N-methyltransferase (PNMT), as well as orexin and tyrosine hydroxylase (TH) were applied to demonstrate the orexinergic innervation of catecholamine cell groups in the lower brainstem of the mouse and the rat. In various densities, networks of orexin-positive fibers and terminals were present on neurons of each adrenaline (C1, C2, C3) and noradrenaline (locus coeruleus, A1, A2, A4, A5 and A7) cell groups. The most dense networks of orexin fibers and terminals were detected in the locus coeruleus, the subcoeruleus area, and in the nucleus of the solitary tract. By using confocal microscope to analyze triple immunostainings we could detect that about two-third of the orexin-PNMT or orexin-TH immunopositive close contacts contained synaptophysin (a presynapse-specific protein) in the C1, C2 and C3 adrenaline, or in the A1, A2 noradrenaline cell groups, respectively. Orexin-immunopositive axons in the C1, C2, as well as A1, A2 and A6 cell groups have been examined by an electron microscope. Relatively few asymmetrical (excitatory) synaptic contacts could be demonstrated between PNMT- or TH-positive dendrites and orexin terminals, although the vast majority of orexin-positive axons was located in juxtaposition to PNMT- or TH-positive neurons.
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PMID:Interactions between orexin-immunoreactive fibers and adrenaline or noradrenaline-expressing neurons of the lower brainstem in rats and mice. 2043 98

To evaluate the contribution of neural pathways to the determination of the circadian oscillator phase in peripheral organs, we assessed lateralization of clock gene expression in Syrian hamsters induced to split rhythms of locomotor activity by exposure to constant light. We measured the ratio of haPer1, haPer2, and haBmal1 mRNA on the high vs. low (H/L) side at 3-h intervals prior to the predicted activity onset (pAO). We also calculated expression on the sides ipsilateral vs. contralateral (I/C) to the side of the suprachiasmatic nucleus (SCN) expressing higher haPer1. The extent of asymmetry in split hamsters varied between specific genes, phases, and organs. Although the magnitude of asymmetry in peripheral organs was never as great as that in the SCN, we observed significantly greater lateralization of clock gene expression in the adrenal medulla and cortex, lung, and skeletal muscle, but not in liver or kidney, of split hamsters than of unsplit controls. We observed fivefold lateralization of expression of the clock-controlled gene, albumin site D-element binding protein (Dbp), in skeletal muscle (H/L: 10.7 +/- 3.7 at 3 h vs. 2.2 +/- 0.3 at 0 h pAO; P = 0.03). Furthermore, tyrosine hydroxylase expression was asymmetrical in the adrenal medulla of split (H/L: 1.9 +/- 0.5 at 0 h) vs. unsplit hamsters (1.2 +/- 0.04; P < 0.05). Consistent with a model of neurally controlled gene expression, we found significant correlations between the phase angle between morning and evening components (psi(me)) and the level of asymmetry (H/L or I/C). Our results indicate that neural pathways contribute to, but cannot completely account for, SCN regulation of the phase of peripheral oscillators.
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PMID:Lateralization of the central circadian pacemaker output: a test of neural control of peripheral oscillator phase. 2059 76

The olfactory bulb (OB) of mammals contains the major endogenous dopamine-producing system in the forebrain. The vast majority of dopaminergic neurons consists of juxtaglomerular cells, which innervate the olfactory glomeruli and modulate the entrance of sensory information to the OB. Although dopaminergic juxtaglomerular cells have been widely investigated, the presence of dopaminergic interneurons other than juxtaglomerular cells has been largely unexplored. In this study, we analyze a population of tyrosine hydroxylase (TH)-containing interneurons located in the external plexiform layer (EPL) of the rat OB. These interneurons are GABAergic and morphologically heterogeneous. They have an axon and two to four dendrites running throughout the EPL. Frequently, they have appendages similar to spines in the dendrites and, sometimes, the distal portions of the dendritic branches show enlargements or swellings similar to varicosities. Contrary to other interneurons of the EPL, the TH-containing ones do not form dendro-dendritic synapses on principal cells and do not receive dendro-dendritic synapses from them. In fact, no synapses were found from the dendrites of these interneurons. When their dendrites are involved in synaptic contacts, they are always the postsynaptic element. They receive symmetrical and asymmetrical synapses from GABAergic and non-GABAergic axons of unidentified origin. Our data indicate that the local circuits of the EPL are more complex than previously thought. Although most of the interneurons of this layer establish dendro-dendritic synaptic relationships with principal cells, the TH-containing interneurons constitute an exception to this rule, resembling interneurons from other cortical areas.
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PMID:Characterization of a population of tyrosine hydroxylase-containing interneurons in the external plexiform layer of the rat olfactory bulb. 2258 98

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