Home About us Contact
|
Home About us Contact | ||
|
|
||
Th
Terms modified by Th Selected AbstractsEarly identification of non-remission in first-episode psychosis in a two-year outcome studyACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2010E. Simonsen Simonsen E, Friis S, Opjordsmoen S, Mortensen EL, Haahr U, Melle I, Joa I, Johannessen JO, Larsen TK, Røssberg JI, Rund BR, Vaglum P, McGlashan TH. Early identification of non-remission in first-episode psychosis in a two-year outcome study. Objective:, To identify predictors of non-remission in first-episode, non-affective psychosis. Method:, During 4 years, we recruited 301 patients consecutively. Information about first remission at 3 months was available for 299 and at 2 years for 293 cases. Symptomatic and social outcomes were assessed at 3 months, 1 and 2 years. Results:, One hundred and twenty-nine patients (43%) remained psychotic at 3 months and 48 patients (16.4%) remained psychotic over 2 years. When we compared premorbid and baseline data for the three groups, the non-remitted (n = 48), remitted for <6 months (n = 38) and for more than 6 months (n = 207), duration of untreated psychosis (DUP) was the only variable that significantly differentiated the groups (median DUP: 25.5, 14.4 and 6.0 weeks, respectively). Three months univariate predictors of non-remission were being single, longer DUP, core schizophrenia, and less excitative and more negative symptoms at baseline. Two-year predictors were younger age, being single and male, deteriorating premorbid social functioning, longer DUP and core schizophrenia. In multivariate analyses DUP, negative and excitative symptoms predicted non-remission at 3 months, but only DUP predicted at 2 years. Conclusion:, Long DUP predicted both 3 month and 2-year non-remission rates in first-episode psychosis. [source] A 2-year follow-up of involuntary admission's influence upon adherence and outcome in first-episode psychosisACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2010S. Opjordsmoen Opjordsmoen S, Friis S, Melle I, Haahr U, Johannessen JO, Larsen TK, Røssberg JI, Rund BR, Simonsen E, Vaglum P, McGlashan TH. A 2-year follow-up of involuntary admission's influence upon adherence and outcome in first-episode psychosis. Objective:, To see, if voluntary admission for treatment in first-episode psychosis results in better adherence to treatment and more favourable outcome than involuntary admission. Method:, We compared consecutively first-admitted, hospitalised patients from a voluntary (n = 91) with an involuntary (n = 126) group as to psychopathology and functioning using Positive and Negative Syndrome Scale and Global Assessment of Functioning Scales at baseline, after 3 months and at 2 year follow-up. Moreover, duration of supportive psychotherapy, medication and number of hospitalisations during the 2 years were measured. Results:, More women than men were admitted involuntarily. Voluntary patients had less psychopathology and better functioning than involuntary patients at baseline. No significant difference as to duration of psychotherapy and medication between groups was found. No significant difference was found as to psychopathology and functioning between voluntarily and involuntarily admitted patients at follow-up. Conclusion:, Legal admission status per se did not seem to influence treatment adherence and outcome. [source] Genistein prevents thyroid hormone-dependent tail regression of Rana catesbeiana tadpoles by targetting protein kinase C and thyroid hormone receptor ,DEVELOPMENTAL DYNAMICS, Issue 3 2007L. Ji Abstract Thyroid hormone (TH)-regulated gene expression is mainly mediated by TH binding to nuclear thyroid hormone receptors (TRs). Despite extensive studies in mammalian cell lines that show that phosphorylation signaling pathways are important in TH action, little is known about their roles on TH signaling in vivo during development. Anuran metamorphosis is a postembryonic process that is absolutely dependent upon TH and tadpole tail resorption can be precociously induced by exogenous administration of 3,5,3,-triiodothyronine (T3). We demonstrate that genistein (a major isoflavone in soy products and tyrosine kinase inhibitor) and the PKC inhibitor (H7) prevent T3 -induced regression of the Rana catesbeiana tadpole tail. T3 -induced protein kinase C tyrosine phosphorylation and kinase activity are inhibited by genistein while T3 -induced up-regulation of TR, mRNA, but not TR, mRNA, is significantly attenuated, most likely through inhibition of T3 -dependent phosphorylation of the TR, protein. This phosphorylation may be modulated through PKC. These data demonstrate that T3 signaling in the context of normal cells in vivo includes phosphorylation as an important factor in establishing T3 -dependent tail regression during development. Developmental Dynamics 236:777,790, 2007. © 2007 Wiley-Liss, Inc. [source] Shh/BMP-4 signaling pathway is essential for intestinal epithelial development during Xenopus larval-to-adult remodelingDEVELOPMENTAL DYNAMICS, Issue 12 2006Atsuko Ishizuya-Oka Abstract During amphibian larval-to-adult intestinal remodeling, progenitor cells of the adult epithelium actively proliferate and differentiate under the control of thyroid hormone (TH) to form the intestinal absorptive epithelium, which is analogous to the mammalian counterpart. We previously found that TH,up-regulated expression of bone morphogenetic protein-4 (BMP-4) spatiotemporally correlates with adult epithelial development in the Xenopus laevis intestine. Here, we aimed to clarify the role of BMP-4 in intestinal remodeling. Our reverse transcriptase-polymerase chain reaction and in situ hybridization analyses indicated that mRNA of BMPR-IA, a type I receptor of BMP-4, is expressed in both the developing connective tissue and progenitor cells of the adult epithelium. More importantly, using organ culture and immunohistochemical procedures, we have shown that BMP-4 not only represses cell proliferation of the connective tissue but promotes differentiation of the intestinal absorptive epithelium. In addition, we found that the connective tissue-specific expression of BMP-4 mRNA is up-regulated by sonic hedgehog (Shh), whose epithelium-specific expression is directly induced by TH. These results strongly suggest that the Shh/BMP-4 signaling pathway plays key roles in the amphibian intestinal remodeling through epithelial,connective tissue interactions. Developmental Dynamics 235:3240,3249, 2006. © 2006 Wiley-Liss, Inc. [source] Ontogeny of tyrosine hydroxylase mRNA expression in mid- and forebrain: Neuromeric pattern and novel positive regionsDEVELOPMENTAL DYNAMICS, Issue 3 2005Faustino Marín Abstract Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of catecholamines and, thus, critical in determining the catecholaminergic phenotype. In this study, we have examined the expression of TH mRNA by in situ hybridization in the embryonic mouse forebrain and midbrain and have mapped its localization according to the neuromeric pattern. We find that early in embryonic development, 10 to 12 days post coitum (dpc), TH mRNA is expressed in ample continuous regions of the neuroepithelium, extending across several neuromeres. However, from 12.5 dpc onward, the expression becomes restricted to discrete regions, which correspond to the dopaminergic nuclei (A8 to A15). In addition to these nuclei previously described, TH mRNA is also observed in regions that do not express this enzyme according to immunohistochemical studies. This difference in relation to protein expression pattern is consequent with the known posttranscriptional regulation of TH expression. The most representative example of a novel positive region is the conspicuous mRNA expression in both medial and lateral ganglionic eminences. This result agrees with reports describing the capacity of striatal stem cells (that is, located at the lateral ganglionic eminence) to become dopaminergic in vitro. Other regions include the isthmic mantle layer and the early floor plate of the midbrain,caudal forebrain. On the whole, the expression map we have obtained opens new perspectives for evolutionary/comparative studies, as well as for therapeutic approaches looking for potentially dopaminergic cells. Developmental Dynamics 234:709,717, 2005. © 2005 Wiley-Liss, Inc. [source] Effects of retinoic acid upon eye field morphogenesis and differentiationDEVELOPMENTAL DYNAMICS, Issue 3 2001Gerald W. Eagleson Abstract This study describes a whole embryo and embryonic field analysis of retinoic acid's (RA) effects upon Xenopus laevis forebrain development and differentiation. By using in situ and immunohistochemical analysis of pax6, Xbf1, and tyrosine hydroxylase (TH), gene expression during eye field, telencephalon field, and retinal development was followed with and without RA treatment. These studies indicated that RA has strong effects upon embryonic eye and telencephalon field development with greater effects upon the ventral development of these organ fields. The specification and determination of separate eye primordia occurred at stage-16 when the prechordal plate reaches its most anterior aspect in Xenopus laevis. Differentiation of the dopaminergic cells within the retina was also affected in a distinct dorsoventral pattern by RA treatment, and cell type differentiation in the absence of distinct retinal laminae was also observed. It was concluded that early RA treatments affected organ field patterning by suppression of the upstream elements required for organ field development, and RA's effects upon cellular differentiation occur downstream to these organ determinants' expression within a distinct dorsoventral pattern. © 2001 Wiley-Liss, Inc. [source] The migratory behavior of immature enteric neuronsDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2009M.M. Hao Abstract While they are migrating caudally along the developing gut, around 10%,20% of enteric neural crest-derived cells start to express pan-neuronal markers and tyrosine hydroxylase (TH). We used explants of gut from embryonic TH-green fluorescence protein (GFP) mice and time-lapse microscopy to examine whether these immature enteric neurons migrate and their mode of migration. In the gut of E10.5 and E11.5 TH-GFP mice, around 50% of immature enteric neurons (GFP+ cells) migrated, with an average speed of around 15 ,m/h. This is slower than the speed at which the population of enteric neural crest-derived cells advances along the developing gut, and hence neuronal differentiation seems to slow, but not necessarily halt, the caudal migration of enteric neural crest cells. Most migrating immature enteric neurons migrated caudally by extending a long-leading process followed by translocation of the cell body. This mode of migration is different from that of non-neuronal enteric neural crest-derived cells and neural crest cells in other locations, but resembles that of migrating neurons in many regions of the developing central nervous system (CNS). In migrating immature enteric neurons, a swelling often preceded the movement of the nucleus in the direction of the leading process. However, the centrosomal marker, pericentrin, was not localized to either the leading process or swelling. This seems to be the first detailed report of neuronal migration in the developing mammalian peripheral nervous system. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2009. [source] Intrastriatal administration of human immunodeficiency virus-1 glycoprotein 120 reduces glial cell-line derived neurotrophic factor levels and causes apoptosis in the substantia nigraDEVELOPMENTAL NEUROBIOLOGY, Issue 12 2006Rachel L. Nosheny Abstract Uninfected neurons of the substantia nigra (SN) degenerate in human immunodeficiency virus (HIV)-positive patients through an unknown etiology. The HIV envelope glycoprotein 120 (gp120) causes apoptotic neuronal cell death in the rodent striatum, but its primary neurotoxic mechanism is still under investigation. Previous studies have shown that gp120 causes neurotoxicity in the rat striatum by reducing brain-derived neurotrophic factor (BDNF). Because glial cell line-derived neurotrophic factor (GDNF) and BDNF are neurotrophic factors crucial for the survival of dopaminergic neurons of the SN, we investigated whether gp120 reduces GDNF and BDNF levels concomitantly to induce apoptosis. Rats received a microinjection of gp120 or vehicle into the striatum and were sacrificed at various time intervals. GDNF but not BDNF immunoreactivity was decreased in the SN by 4 days in gp120-treated rats. In these animals, a significant increase in the number of caspase-3- positive neurons, both tyrosine hydroxylase (TH)-positive and -negative, was observed. Analysis of TH immunoreactivity revealed fewer TH-positive neurons and fibers in a medial and lateral portion of cell group A9 of the SN, an area that projects to the striatum, suggesting that gp120 induces retrograde degeneration of nigrostriatal neurons. We propose that dysfunction of the nigrostriatal dopaminergic system associated with HIV may be caused by a reduction of neurotrophic factor expression by gp120. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Early and transient ontogenetic expression of the cocaine- and amphetamine-regulated transcript peptide in the rat mesencephalon: Correlation with tyrosine hydroxylase expressionDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2002F. Brischoux Abstract The ontogeny of cocaine- and amphetamine-regulated transcript (CART) expression has been analyzed by immunohistochemistry in the mesencephalon of the rat central nervous system, and compared to the pattern of tyrosine hydroxylase- (TH-) expression. CART-producing neurons were first detected on the embryonic day 11 (E11) in the ventral mesencephalic vesicle. These neurons are among the first cells of the mantle layer to differentiate. From E13, a complementary pattern of distribution was observed, dividing the mantle layer into an external TH zone and an internal CART zone. Many TH-positive neurons were found to migrate from the neuroepithelium through the area containing the CART-immunoreactive neurons to settle more laterally. These TH cells exhibited prominent leading and trailing dendrites in the immediate vicinity of CART perikarya. On E16, the number of CART neurons appeared to diminish, and they were confined near the ventricle and around the fasciculus retroflexus. On E18 and E20, only the Edinger-Westphal nucleus exhibited a strong CART staining as described in the adult brain. Thus, the very early detection of CART during prenatal ontogeny led us to speculate that this peptide might have a role in the development of specific regions of the rat brain. In particular, our observations suggest that CART-expressing neurons might help the migration of the dopaminergic neurons of the substantia nigra. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 221,229, 2002 [source] Metamorphic inhibition of Xenopus laevis by sodium perchlorate: Effects on development and thyroid histologyENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2005Joseph E. Tietge Abstract The perchlorate anion inhibits thyroid hormone (TH) synthesis via inhibition of the sodium-iodide symporter. It is, therefore, a good model chemical to aid in the development of a bioassay to screen chemicals for affects on thyroid function. Xenopus laevis larvae were exposed to sodium perchlorate during metamorphosis, a period of TH-dependent development, in two experiments. In the first experiment, stage 51 and 54 larvae were exposed for 14 d to 16, 63, 250, 1,000, and 4,000 ,g perchlorate/L. In the second experiment, stage 51 larvae were exposed throughout metamorphosis to 8, 16, 32, 63, and 125 ,g perchlorate/L. Metamorphic development and thyroid histology were the primary endpoints examined. Metamorphosis was retarded significantly in the first study at concentrations of 250 ,g/L and higher, but histological effects were observed at 16 ,g/L. In the second study, metamorphosis was delayed by 125 ,g/L and thyroid size was increased significantly at 63 ,g/L. These studies demonstrate that inhibition of metamorphosis readily can be detected using an abbreviated protocol. However, thyroid gland effects occur at concentrations below those required to elicit developmental delay, demonstrating the sensitivity of this endpoint and suggesting that thyroidal compensation is sufficient to promote normal development until perchlorate reaches critical concentrations. [source] Age-matched lymphocyte subpopulation reference values in childhood and adolescence: application of exponential regression analysisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2008Sabine Huenecke Abstract Background:, Normal values of lymphocyte subpopulations for healthy children and adults have been published in defined age groups exclusively, which results in difficult data interpretation for patients close to the limit of contiguous age group ranges. In addition, normal values for a number of lymphocyte subpopulations have not been established to date. Objective:, The aim of this study was to develop a model which provides continuous age-dependent reference values. This model was applied for lymphocyte subpopulations such as naïve and memory T cells as well as their activation profile with diagnostic relevance in children and adults. Study design:, A total of 100 blood samples, obtained from 80 healthy children and 20 adults were analysed by means of four colour-flow cytometry. Continuous age-dependent reference values were computed based on the residual values in an exponential regression model. Results:, We calculated a continuous age-related regression model for both, absolute cell counts and percentages of CD3+CD4+ T helper (TH) cells, CD3+CD8+ cytotoxic T cells, CD56+CD3, natural killer (NK) cells, CD56+CD3+ T cells, CD3+CD4+CD45RA+ naïve TH cells, CD3+CD4+CD45RO+ memory TH cells, CD3+CD8+CD45RA+CD28+ naïve cytotoxic T cells, CD3+CD8+CD45RO+ memory cytotoxic T cells, CD3+CD8+CD69+ early activated cytotoxic T cells and CD3+CD8+HLA-DR+ late activated cytotoxic T cells, respectively, to obtain reference values. Conclusion:, Based on an exponential regression model, the obtained reference values reflect the continuous maturation of lymphocyte subsets during childhood. [source] PRECLINICAL STUDY: FULL ARTICLE: Altered architecture and functional consequences of the mesolimbic dopamine system in cannabis dependenceADDICTION BIOLOGY, Issue 3 2010Saturnino Spiga ABSTRACT Cannabinoid withdrawal produces a hypofunction of mesencephalic dopamine neurons that impinge upon medium spiny neurons (MSN) of the forebrain. After chronic treatment with two structurally different cannabinoid agonists, ,9 -tetrahydrocannabinol and CP55 940 (CP) rats were withdrawn spontaneously and pharmacologically with the CB1 antagonist SR141716A (SR). In these two conditions, evaluation of tyrosine hydroxylase (TH)-positive neurons revealed significant morphometrical reductions in the ventrotegmental area but not substantia nigra pars compacta of withdrawn rats. Similarly, confocal analysis of Golgi,Cox-stained sections of the nucleus accumbens revealed a decrease in the shell, but not the core, of the spines' density of withdrawn rats. Administration of the CB1 antagonist SR to control rats, provoked structural abnormalities reminiscent of those observed in withdrawal conditions and support the regulatory role of cannabinoids in neurogenesis, axonal growth and synaptogenesis by acting as eu-proliferative signals through the CB1 receptors. Further, these measures were incorporated into a realistic computational model that predicts a strong reduction in the excitability of morphologically altered MSN, yielding a significant reduction in action potential output. These pieces of evidence support the tenet that withdrawal from addictive compounds alters functioning of the mesolimbic system and provide direct morphological evidence for functional abnormalities associated with cannabinoid dependence at the level of dopaminergic neurons and their postsynaptic counterpart and are coherent with recent hypothesis underscoring a hypodopaminergic state as a distinctive feature of the ,addicted brain'. [source] Low frequency of Parkin, Tyrosine Hydroxylase, and GTP Cyclohydrolase I gene mutations in a Danish population of early-onset Parkinson's DiseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2006J. M. Hertz Autosomal recessive Parkinson's disease (PD) with early-onset may be caused by mutations in the parkin gene (PARK2). We have ascertained 87 Danish patients with an early-onset form of PD (age at onset ,40 years, or ,50 years if family history is positive) in a multicenter study in order to determine the frequency of PARK2 mutations. Analysis of the GTP cyclohydrolase I gene (GCH1) and the tyrosine hydroxylase gene (TH), mutated in dopa-responsive dystonia and juvenile PD, have also been included. Ten different PARK2 mutations were identified in 10 patients. Two of the patients (2.3%) were found to have homozygous or compound heterozygous mutations, and eight of the patients (9.2%) were found to be heterozygous. A mutation has been identified in 10.4% of the sporadic cases and in 15.0% of cases with a positive family history of PD. One patient was found to be heterozygous for both a PARK2 mutation and a missense mutation (A6T) in TH of unknown significance. It cannot be excluded that both mutations contribute to the phenotype. No other putative disease causing TH or GCH1 mutations were found. In conclusion, homozygous, or compound heterozygous PARK2 mutations, and mutations in GCH1 and TH, are rare even in a population of PD patients with early-onset of the disease. [source] PPAR-gamma-mediated neuroprotection in a chronic mouse model of Parkinson's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2009Nicoletta Schintu Abstract Rosiglitazone is a commonly prescribed insulin-sensitizing drug with a selective agonistic activity on the peroxisome proliferator-activated receptor-gamma (PPAR-,). PPAR-, can modulate inflammatory responses in the brain, and agonists might be beneficial in neurodegenerative diseases. In the present study we used a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine plus probenecid (MPTPp) mouse model of progressive Parkinson's disease (PD) to assess the therapeutic efficacy of rosiglitazone on behavioural impairment, neurodegeneration and inflammation. Mice chronically treated with MPTPp displayed typical features of PD, including impairment of motor and olfactory functions associated with partial loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc), decrease of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) content and dynorphin (Dyn) mRNA levels in the caudate-putamen (CPu), intense microglial and astroglial response in the SNc and CPu. Chronic rosiglitazone, administered in association with MPTPp, completely prevented motor and olfactory dysfunctions and loss of TH-positive cells in the SNc. In the CPu, loss of striatal DA was partially prevented, whereas decreases in DOPAC content and Dyn were fully counteracted. Moreover, rosiglitazone completely inhibited microglia reactivity in SNc and CPu, as measured by CD11b immunostaining, and partially inhibited astroglial response assessed by glial fibrillary acidic protein immunoreactivity. Measurement of striatal MPP+ levels 2, 4, 6 h and 3 days after chronic treatment indicated that MPTP metabolism was not altered by rosiglitazone. The results support the use of PPAR-, agonists as a putative anti-inflammatory therapy aimed at arresting PD progression, and suggest that assessment in PD clinical trials is warranted. [source] Light regulation of retinal dopamine that is independent of melanopsin phototransductionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2009M. A. Cameron Abstract Light-dependent release of dopamine (DA) in the retina is an important component of light-adaptation mechanisms. Melanopsin-containing inner retinal photoreceptors have been shown to make physical contacts with DA amacrine cells, and have been implicated in the regulation of the local retinal environment in both physiological and anatomical studies. Here we determined whether they contribute to photic regulation of DA in the retina as assayed by the ratio of DA with its primary metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), and by c-fos induction in tyrosine hydroxylase (TH)-labelled DA amacrine cells. Light treatment (,0.7 log W/m2 for 90 min) resulted in a substantial increase in DA release (as revealed by an increase in the DOPAC : DA ratio), as well as widespread induction of nuclear c-fos in DA amacrine cells in wild-type mice and in mice lacking melanopsin (Opn4,/,). Light-induced DA release was also retained in mice lacking rod phototransduction (Gnat1,/,), although the magnitude of this response was substantially reduced compared with wild-types, as was the incidence of light-dependent nuclear c-fos in DAergic amacrines. By contrast, the DAergic system of mice lacking both rods and cones (rd/rd cl) showed no detectable light response. Our data suggest that light regulation of DA, a pivotal retinal neuromodulator, originates primarily with rods and cones, and that melanopsin is neither necessary nor sufficient for this photoresponse. [source] Glutamatergic neurons are present in the rat ventral tegmental areaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2007Tsuyoshi Yamaguchi Abstract The ventral tegmental area (VTA) is thought to play an important role in reward function. Two populations of neurons, containing either dopamine (DA) or ,-amino butyric acid (GABA), have been extensively characterized in this area. However, recent electrophysiological studies are consistent with the notion that neurons that utilize neurotransmitters other than DA or GABA are likely to be present in the VTA. Given the pronounced phenotypic diversity of neurons in this region, we have proposed that additional cell types, such as those that express the neurotransmitter glutamate may also be present in this area. Thus, by using in situ hybridization histochemistry we investigated whether transcripts encoded by genes for the two vesicular glutamate transporters, VGluT1 or VGluT2, were expressed in the VTA. We found that VGluT2 mRNA but not VGluT1 mRNA is expressed in the VTA. Neurons expressing VGluT2 mRNA were differentially distributed throughout the rostro-caudal and medio-lateral aspects of the VTA, with the highest concentration detected in rostro-medial areas. Phenotypic characterization with double in situ hybridization of these neurons indicated that they rarely co,expressed mRNAs for tyrosine hydroxylase (TH, marker for DAergic neurons) or glutamic acid decarboxylase (GAD, marker for GABAergic neurons). Based on the results described here, we concluded that the VTA contains glutamatergic neurons that in their vast majority are clearly non-DAergic and non-GABAergic. [source] A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosetsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Mahmoud M. Iravani Abstract Standard MPTP treatment regimens in primates result in >,85% destruction of nigral dopaminergic neurons and the onset of marked motor deficits that respond to known symptomatic treatments for Parkinson's disease (PD). The extent of nigral degeneration reflects the late stages of PD rather than events occurring at its onset. We report on a modified MPTP treatment regimen that causes nigral dopaminergic degeneration in common marmosets equivalent to that occurring at the time of initiation of motor symptoms in man. Subcutaneous administration of MPTP 1 mg/kg for 3 consecutive days caused a reproducible 60% loss of nigral tyrosine hydroxylase (TH)-positive cells, which occurred mainly in the calbindin-D28k -poor nigrosomes with a similar loss of TH-immunoreactivity (TH-ir) in the caudate nucleus and the putamen. The animals showed obvious motor abnormalities with reduced bursts of activity and the onset of motor disability. However, the loss of striatal terminals did not reflect early PD because a greater loss of TH-ir occurred in the caudate nucleus than in the putamen and a marked reduction in TH-ir occurred in striatal patches compared to the matrix. Examination of striatal fibres following a partial MPTP lesion showed a conspicuous increase in the number and the diameter of large branching fibres in the putaminal and to some extent caudatal matrix, pointing to a possible compensatory sprouting of dopaminergic terminals. In addition, these partially lesioned animals did not respond to acute treatment with L-DOPA. This primate partial lesions model may be useful for examining potential neuroprotective or neurorestorative agents for PD. [source] Tyrosine hydroxylase-positive neurons intrinsic to the human striatum express the transcription factor Nurr1EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2004Martine Cossette Abstract The putative dopaminergic (DA) neurons intrinsic to human striatum were studied to determine their similarity with DA neurons of the substantia nigra pars compacta (SNpc). The comparison was based on morphological features and on the presence or absence of Nurr1, an orphan receptor of the nuclear receptor family that is essential for the expression of DA phenotype by developing SNpc neurons. Immunohistochemistry for the neuronal nuclear protein (NeuN; a neuronal marker) and in situ hybridization for tyrosine hydroxylase (TH) and/or Nurr1 were applied to post-mortem tissue obtained from seven normal individuals. On one hand, the TH-positive multipolar neurons in the human striatum, which were subdivided into three groups according to their size and pattern of dendritic arborization, were found to be morphologically similar to TH-positive neurons of the SNpc. The distribution frequency of striatal TH-positive neurons, according to their diameter, closely matches the frequency observed for multipolar TH-positive cells in the SNpc. On the other hand, the proportion of neurons expressing Nurr1 and TH mRNA transcripts on single striatal section was similar to the proportion of TH-immunoreactive neurons observed on adjacent sections. More importantly, in each striatum analysed, virtually all cells that stained for TH also expressed NeuN and Nurr1. This study provides novel data that confirm the existence of DA neurons intrinsic to the human striatum. It also provides the first evidence for the existence of striking morphological and chemical similarities between the DA neurons present at striatal level and those that populate the SNpc. [source] Synaptic release of dopamine in the subthalamic nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2004Stephanie J. Cragg Abstract The direct modulation of subthalamic nucleus (STN) neurons by dopamine (DA) neurons of the substantia nigra (SN) is controversial owing to the thick caliber and low density of DA axons in the STN. The abnormal activity of the STN in Parkinson's disease (PD), which is central to the appearance of symptoms, is therefore thought to result from the loss of DA in the striatum. We carried out three experiments in rats to explore the function of DA in the STN: (i) light and electron microscopic analysis of tyrosine hydroxylase (TH)-, dopamine ,-hydroxylase (D,H)- and DA-immunoreactive structures to determine whether DA axons form synapses; (ii) fast-scan cyclic voltammetry (FCV) to determine whether DA axons release DA; and (iii) patch clamp recording to determine whether DA, at a concentration similar to that detected by FCV, can modulate activity and synaptic transmission/integration. TH- and DA-immunoreactive axons mostly formed symmetric synapses. Because D,H-immunoreactive axons were rare and formed asymmetric synapses, they comprised the minority of TH-immunoreactive synapses. Voltammetry demonstrated that DA release was sufficient for the activation of receptors and abolished by blockade of voltage-dependent Na+ channels or removal of extracellular Ca2+. The lifetime and concentration of extracellular DA was increased by blockade of the DA transporter. Dopamine application depolarized STN neurons, increased their frequency of activity and reduced the impact of ,-aminobutyric acid (GABA)-ergic inputs. These findings suggest that SN DA neurons directly modulate the activity of STN neurons and their loss may contribute to the abnormal activity of STN neurons in PD. [source] Involvement of Nurr1 in specifying the neurotransmitter identity of ventral midbrain dopaminergic neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2003Simone M. Smits Abstract The mesencephalic dopaminergic (mesDA) system is involved in many brain functions including motor control and motivated behaviour, and is of clinical importance because of its implication in psychiatric disorders and Parkinson's disease. Nurr1, a member of the nuclear hormone receptor superfamily of transcription factors, is essential for establishing the dopaminergic phenotype, because expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, requires Nurr1. In addition, Nurr1 plays an important role in the maintenance of mesDA neurons. Neonatal Nurr1 knockout mice lack expression of the dopamine transporter (DAT), the vesicular monoamine transporter 2 (VMAT2) and l -aromatic amino acid decarboxylase (AADC) in addition to TH specifically in mesDA neurons. It is unclear whether the lack of expression of these dopaminergic markers is caused by a maintenance defect or whether the induction of these markers depends on Nurr1 expression. To address this problem, the expression of DAT, VMAT2 and AADC was analysed at embryonic day 12.5 and 14.5. Here we demonstrate that induction of VMAT2 and DAT specifically in mesDA neurons requires Nurr1 expression, whereas AADC expression in mesDA neurons is induced independently of Nurr1 function. [source] Acute and long-term changes in the mesolimbic dopamine pathway after systemic or local single nicotine injectionsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002R. Ferrari Abstract We have examined several neurochemical and behavioural parameters related to the function of the mesolimbic dopamine (DA) pathway in animals treated with nicotine following three modes of drug administration, i.e. systemic intraperitoneal injection, intra-accumbens (Acb) infusion or intraventral tegmental area (intra-VTA) microinjection. The present modes of systemic, intra-Acb and intra-VTA nicotine administration elicited comparable acute increases in dialysate DA levels from the Acb. The increase in extracellular DA levels was paralleled by a significant enhancement of locomotion in a habituated environment in the case of systemic or intra-VTA nicotine administration, whereas unilateral or bilateral intra-Acb nicotine infusion was ineffective, showing that accumbal DA increase is not sufficient to elicit locomotion in this experimental paradigm. Intra-VTA, but not systemic or intra-Acb, nicotine administration caused a long-term (at least 24-h) increase in basal dialysate DA levels from the Acb. In addition, significant increases in tyrosine hydroxylase (TH) and GluR1 (but not dopamine transporter or NR1) mRNA levels in the VTA were detected 24 h after intra-VTA nicotine administration. Systemic nicotine injection caused only an increase in TH mRNA levels while intra-Acb infusion did not modify any of the mRNAs tested. The long-term increase in basal DA levels in the Acb and TH, and GluR1 mRNA levels in the VTA upon intra-VTA nicotine microinjection indicates that even a single nicotine injection can induce plastic changes of the mesolimbic DA pathway. [source] O2 -sensing after carotid chemodenervation: hypoxic ventilatory responsiveness and upregulation of tyrosine hydroxylase mRNA in brainstem catecholaminergic cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2000Jean-Christophe Roux Abstract Ventilatory responses to acute and long-term hypoxia are classically triggered by carotid chemoreceptors. The chemosensory inputs are carried within the carotid sinus nerve to the nucleus tractus solitarius and the brainstem respiratory centres. To investigate whether hypoxia acts directly on brainstem neurons or secondarily via carotid body inputs, we tested the ventilatory responses to acute and long-term hypoxia in rats with bilaterally transected carotid sinus nerves and in sham-operated rats. Because brainstem catecholaminergic neurons are part of the chemoreflex pathway, the ventilatory response to hypoxia was studied in association with the expression of tyrosine hydroxylase (TH). TH mRNA levels were assessed in the brainstem by in situ hybridization and hypoxic ventilatory responses were measured in vivo by plethysmography. After long-term hypoxia, TH mRNA levels in the nucleus tractus solitarius and ventrolateral medulla increased similarly in chemodenervated and sham-operated rats. Ventilatory acclimatization to hypoxia developed in chemodenervated rats, but to a lesser extent than in sham-operated rats. Ventilatory response to acute hypoxia, which was initially low in chemodenervated rats, was fully restored within 21 days in long-term hypoxic rats, as well as in normoxic animals which do not overexpress TH. Therefore, activation of brainstem catecholaminergic neurons and ventilatory adjustments to hypoxia occurred independently of carotid chemosensory inputs. O2 -sensing mechanisms unmasked by carotid chemodenervation triggered two ventilatory adjustments: (i) a partial acclimatization to long-term hypoxia associated with TH upregulation; (ii) a complete restoration of acute hypoxic responsivity independent of TH upregulation. [source] Novel regulation of yolk utilization by thyroid hormone in embryos of the direct developing frog Eleutherodactylus coquiEVOLUTION AND DEVELOPMENT, Issue 5 2010Srikanth Singamsetty SUMMARY Thyroid hormone (TH) is required for metamorphosis of the long, coiled tadpole gut into the short frog gut. Eleutherodactylus coqui, a direct developing frog, lacks a tadpole. Its embryonic gut is a miniature adult form with a mass of yolky cells, called nutritional endoderm, attached to the small intestine. We tested the TH requirement for gut development in E. coqui. Inhibition of TH synthesis with methimazole arrested gut development in its embryonic form. Embryos treated with methimazole failed to utilize the yolk in their nutritional endoderm, and survived for weeks without further development. Conversely, methimazole and 3,3,,5-tri-iodo- l -thyronine, the active form of TH, stimulated gut development and utilization and disappearance of the nutritional endoderm. In Xenopus laevis, the receptor for TH, TR,, is upregulated in response to TH. Similarly, EcTR,, the E. coqui ortholog, was upregulated by TH in the gut. EcTR, expression was high in the nutritional endoderm, suggesting a direct role for TH in yolk utilization by these cells. An initial step in the breakdown of yolk in X. laevis is acidification of the yolk platelet. E. coqui embryos in methimazole failed to acidify their yolk platelets, but acidification was stimulated by TH indicating its role in an early step of yolk utilization. In addition to a conserved TH role in gut development, a novel regulatory role for TH in yolk utilization has evolved in these direct developers. [source] Co-operative effect of the isoforms of type III antifreeze protein expressed in Notched-fin eelpout, Zoarces elongatus KnerFEBS JOURNAL, Issue 2 2005Yoshiyuki Nishimiya We found that Notched-fin eelpout, which lives off the north east coast of Japan, expresses an antifreeze protein (AFP). The liver of this fish contains DNAs that encode at least 13 type III AFP isoforms (denoted nfeAFPs). The primary sequences of the nfeAFP isoforms were categorized into SP- and QAE-sephadex binding groups, and the latter were further divided into two subgroups, QAE1 and QAE2 groups. Ice crystals observed in HPLC-pure nfeAFP fractions are bipyramidal in shape with different ratios of c and a axes, suggesting that all the isoforms are able to bind ice. We expressed five recombinant isoforms of nfeAFP and analyzed the thermal hysteresis (TH) activity of each as a function of protein concentration. We also examined the change in activity on mixing the isoforms. TH was estimated to be 0.60 °C for the QAE1 isoform, 0.11 °C for QAE2, and almost zero for the SP isoforms when the concentrations of these isoforms was standardized to 1.0 mm. Significantly, the TH activity of the SP isoforms showed concentration dependence in the presence of 0.2 mm QAE1, indicating that the less active SP isoform becomes ,active' when a small amount of QAE1 is added. In contrast, it does not become active on the addition of another SP isoform. These results suggest that the SP and QAE isoforms of type III AFP have different levels of TH activity, and they accomplish the antifreeze function in a co-operative manner. [source] Investigation of 17 candidate genes for personality traits confirms effects of the HTR2A gene on novelty seekingGENES, BRAIN AND BEHAVIOR, Issue 4 2009A. Heck Genes involved in serotonergic and dopaminergic neurotransmission have been hypothesized to affect different aspects of personality, but findings from genetic association studies did not provide conclusive results so far. In previous studies, however, only one or a few polymorphisms within single genes were investigated neglecting the possibility that the genetic associations might be more complex comprising several genes or gene regions. To overcome this limitation, we performed an extended genetic association study analyzing 17 serotonergic (SLC6A4, HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR6, MAOA, TPH1, TPH2) and dopaminergic genes (SLC6A3, DRD2, DRD3, DRD4, COMT, MAOA, TH, DBH), which have been previously reported to be implicated with personality traits. One hundred and ninety-five single nucleotide polymorphisms (SNPs) within these genes were genotyped with the Illumina BeadChip technology (HumanHap300, Human-1) in a sample of 366 mentally healthy Caucasians. Additionally, we tried to replicate our results in an independent sample of further 335 Caucasians. Personality traits in both samples were assessed with the German version of Cloninger's Tridimensional Personality Questionnaire. From 30 SNPs showing associations at a nominal level of significance, two intronic SNPs, rs2770296 and rs927544, both located in the HTR2A gene, withstood correction for multiple testing. These SNPs were associated with the personality trait novelty seeking. The effect of rs927544 could be replicated for the novelty seeking subscale extravagance, and the same SNP was also associated with extravagance inthe combined samples. Our results show that HTR2A polymorphisms modulate facets of novelty seeking behaviour in healthy adults suggesting that serotonergic neurotransmission is involved in this phenotype. [source] The history of a developmental stage: Metamorphosis in chordatesGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 11 2008Mathilde Paris Abstract Metamorphosis displays a striking diversity in chordates, a deuterostome phylum that comprises vertebrates, urochordates (tunicates), and cephalochordates (amphioxus). In anuran amphibians, the tadpole loses its tail, develops limbs, and undergoes profound changes at the behavioral, physiological, biochemical, and ecological levels. In ascidian tunicates, the tail is lost and the head tissues are drastically remodeled into the adult animal, whereas in amphioxus, the highly asymmetric larva transforms into a relatively symmetric adult. This wide diversity has led to the proposal that metamorphosis evolved several times independently in the different chordate lineages during evolution. However, the molecular mechanisms involved in metamorphosis are largely unknown outside amphibians and teleost fishes, in which metamorphosis is regulated by the thyroid hormones (TH) T3 and T4 binding to their receptors (thyroid hormone receptors). In this review, we compare metamorphosis in chordates and then propose a unifying definition of the larva-to-adult transition, based on the conservation of the role of THs and some of their derivatives as the main regulators of metamorphosis. According to this definition, all chordates (if not, all deuterostomes) have a homologous metamorphosis stage during their postembryonic development. The intensity and the nature of the morphological remodeling varies extensively among taxa, from drastic remodeling like in some ascidians or amphibians to more subtle events, as in mammals. genesis 46:657,672, 2008. © 2008 Wiley-Liss, Inc. [source] Transgenic expression of Cre recombinase from the tyrosine hydroxylase locusGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 2 2004Jonas Lindeberg Abstract Catecholaminergic neurons are affected in several neurological and psychiatric diseases. Tyrosine hydroxylase (TH) is the first, rate-limiting enzyme in catecholamine synthesis. We report a knockin mouse expressing Cre-recombinase from the 3,-untranslated region of the endogenous Th gene by means of an internal ribosomal entry sequence (IRES). The resulting Cre expression matches the normal pattern of TH expression, while the pattern and level of TH are not altered in the knockin mouse. Crossings with two different LacZ reporter mice demonstrated Cre-mediated genomic recombination in TH expressing tissues. In addition, LacZ was found in some unexpected cell populations (including oocytes), indicating recombination due to transient developmental TH expression. Our novel knockin mouse can be used for generation of tissue-specific or general knockouts (depending on scheme of crossing) in mice carrying genes flanked by loxP sites. This knockin mouse can also be used for tracing cell lineages expressing TH during development. genesis 40:67,73, 2004. © 2004 Wiley-Liss, Inc. [source] Clinical and operative management of persistent hyperparathyroidism after renal transplantation: A single-center experienceHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2007Hanna Gilat MD Abstract Background. Persistent (tertiary) hyperparathyroidism (TH) after renal transplantation may cause considerable morbidity and necessitate parathyroidectomy. This study investigated the characteristics of this patient subgroup. Methods. The medical data and pathology specimens of 20 kidney transplant recipients who underwent parathyroidectomy for TH in 2001 to 2004 were reviewed. Results. Treatment consisted of subtotal resection of 3.5 glands in 13 patients, resection of 3 to 3.5 glands under intraoperative parathyroid hormone monitoring (iPTH) in 5 patients, and selective resection in 2 patients with markedly asymmetric gland enlargement. Eighteen patients had hyperplasia,diffuse in 10, nodular in 4, or both in 2; 2 patients had 1 large nodule in every gland. Six patients had postoperative complications. Follow-up of 2 years revealed recurrent hypercalcemia in 1 patient and a high level of PTH (>60 pg/mL) in 12. Conclusion. Subtotal resection for TH may be insufficient. The use of iPTH monitoring is recommended. Renal transplant recipients have distinctive characteristics and require special perioperative attention. © 2007 Wiley Periodicals, Inc. Head Neck, 2007 [source] Mutations in human monoamine-related neurotransmitter pathway genes,HUMAN MUTATION, Issue 7 2008Jan Haavik Abstract Biosynthesis and metabolism of serotonin and catecholamines involve at least eight individual enzymes that are mainly expressed in tissues derived from the neuroectoderm, e.g., the central nervous system (CNS), pineal gland, adrenal medulla, enterochromaffin tissue, sympathetic nerves, and ganglia. Some of the enzymes appear to have additional biological functions and are also expressed in the heart and various other internal organs. The biosynthetic enzymes are tyrosine hydroxylase (TH), tryptophan hydroxylases type 1 and 2 (TPH1, TPH2), aromatic amino acid decarboxylase (AADC), dopamine beta-hydroxylase (D,H), and phenylethanolamine N -methyltransferase (PNMT), and the specific catabolic enzymes are monoamine oxidase A (MAO-A) and catechol O -methyltransferase (COMT). For the TH, DDC, DBH, and MAOA genes, many single nucleotide polymorphisms (SNPs) with unknown function, and small but increasing numbers of cases with autosomal recessive mutations have been recognized. For the remaining genes (TPH1, TPH2, PNMT, and COMT) several different genetic markers have been suggested to be associated with regulation of mood, pain perception, and aggression, as well as psychiatric disturbances such as schizophrenia, depression, suicidality, and attention deficit/hyperactivity disorder. The genetic markers may either have a functional role of their own, or be closely linked to other unknown functional variants. In the future, molecular testing may become important for the diagnosis of such conditions. Here we present an overview on mutations and polymorphisms in the group of genes encoding monoamine neurotransmitter metabolizing enzymes. At the same time we propose a unified nomenclature for the nucleic acid aberrations in these genes. New variations or details on mutations will be updated in the Pediatric Neurotransmitter Disorder Data Base (PNDDB) database (www.bioPKU.org). Hum Mutat 29(7), 891,902, 2008. © 2008 Wiley-Liss, Inc. [source] Fabrication and Application of an Oxide Thermoelectric SystemINTERNATIONAL JOURNAL OF APPLIED CERAMIC TECHNOLOGY, Issue 4 2007Ryoji Funahashi A plate-shaped thermoelectric module was prepared using 140 pairs of p -type Ca3Co4O9 (Co-349) and n -type LaNiO3 (Ni-113) bulks. The hot-pressed thermoelectric oxide bulks were connected with an Ag paste, incorporating oxide powder, and Ag sheets. The module's open-circuit voltage increases with increasing hot-side temperature (TH) and reaches 4.5 V at a TH of 1072 K in air. No deterioration in output power was seen when power generation was carried out 10 times at a TH of 723 K with intermediate cooling to room temperature. The module was successfully used to charge a lithium-ion battery in a mobile phone. Thermoelectric modules composed of p -type Co-349 and n -type CaMnO3 (Mn-113) bulks, which have a pipe shape, were constructed using Ag electrodes and stainless-steel tubes. The devices were connected with the stainless-steel tube coated with ZrO2 by thermal spray using a dielectric paste composed of silica glass and iron oxide. Power generation was carried out in flame by combustion of natural gas. Water flowed inside the stainless-steel tube for cooling. One module consisting of 54 pairs of legs can generate 1.5 V, 0.28 W, and steam simultaneously by installing in an instantaneous water heater. Power generation was carried out four times with intermediate cooling. Deterioration in the open-circuit voltage of the module was not observed after the fourth combustion. [source] | |||||||||||||||||||||||||||||||||||||||||||