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Catecholaminergic Neurons (catecholaminergic + neuron)
Selected AbstractsTransgenic 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] 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] Noxp20 and Noxp70, two new markers of early neuronal differentiation, detected in teratocarcinoma-derived neuroectodermic precursor cellsJOURNAL OF NEUROCHEMISTRY, Issue 2 2006M. Boucquey Abstract The murine 1C11 cell line, derived from F9 pluripotent teratocarcinoma cells, exhibits features of a bipotential neuronal precursor as it converts into serotonergic or catecholaminergic neurons under appropriate induction. In order to point out molecular markers expressed in this early neuroectodermic commitment, we used a cDNA subtractive hybridization method. The 105 different isolated cDNAs represented 75 known genes, expressed sequence tags (EST) or genomic fragments. A majority of known proteins encoded by these sequences are involved in cellular mobility or migration. We characterized two sequences showing identities with ESTs and we called them Noxp20 and Noxp70. The Noxp20 transcript encodes a putative protein with a predicted caspase recruitment domain and the Noxp70 transcript encodes a putative protein displaying a Zn-finger domain. Consistent with their roles in neuronal cell development, in situ hybridization showed that Noxp20 and Noxp70 are over-expressed in brain. At embryonic days 12 and 15, Noxp20 is strongly expressed in the ventricular and intermediate zones of the brain and of the spinal cord. At embryonic day 15, Noxp70 was found to be strongly expressed in the ventricular zone around the telencephalic ventricle, and to a lower extent in the thalamus and hypothalamus. At post-natal day 10, Noxp20 mRNA was detected in the dentate gyrus, the hippocampus, the cerebellum and the olfactory bulb. [source] Normal nigrostriatal innervation but dopamine dysfunction in mice carrying hypomorphic tyrosine hydroxylase allelesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2003Susanna Althini Abstract We investigated the use of the mouse tyrosine hydroxylase (TH) gene to drive knock-in constructs in catecholaminergic neurons. Two targeting constructs representing truncated forms of either of the BMP receptors ALK-2 or BMPR-II preceded by an internal ribosome entry site (IRES) were introduced into the 3, untranslated region of TH. An frt-flanked neomycin-resistance (neor) cassette was placed in the 3, end of the targeting constructs. Mice homozygous for the knock-in alleles showed various degrees of hypokinetic behavior, depending mainly on whether the neor cassette was removed. In situ hybridization and immunohistochemistry showed that TH mRNA and protein were variously down-regulated in these mouse strains. Reduced levels of dopamine and noradrenalin were found in several brain areas. However, number and morphology of neurons in substantia nigra and their projections to striatum appeared normal in the neor -positive TH hypomorphic mice as examined by markers for L-aromatic amino acid decarboxylase and the dopamine transporter. Elimination of the neor cassette from the knock-in alleles partially restored TH and dopamine levels. The present neor -positive TH hypomorphic mice show that nigrostriatal innervation develops independently of TH and should find use as a model for conditions of reduced catecholamine synthesis, as seen in, for example, L-dihydroxyphenylalanine-responsive dystonia/infantile parkinsonism. © 2003 Wiley-Liss, Inc. [source] The pedunculopontine nucleus in developmental disorders of the basal gangliaNEUROPATHOLOGY, Issue 3 2008Yuki Anzai The pedunculopontine nucleus (PPN), which is located in the upper brainstem, contains cholinergic and non-cholinergic neurons, and has afferent and efferent connections to the basal ganglia and spinal cord. The PPN is known to be affected in adult-onset basal ganglia diseases, and we speculated that the PPN might be similarly insulted in developmental basal ganglia disorders. We immunohistochemically examined the expression patterns of acetylcholine esterase and tyrosine hydroxylase, markers of acetylcholinergic and catecholaminergic neurons, respectively, in the PPN pars dissipata (PPNd) of controls and patients with bilirubin encephalopathy (BE) and perinatal hypoxic ischemic encephalopathy with localized basal ganglia lesion (HIEbg). Controls showed an age-dependent change in the percentages of acetylcholinergic and catecholaminergic neurons. Three out of six BE cases and three out of six HIEbg cases showed a reduction in the percentage of acetylcholinergic neurons in the PPNd. Additionally, three BE cases demonstrated an increase in the percentage of catecholaminergic neurons. It is likely that the relative proportions of acetylcholinergic and catecholaminergic neurons in the PPN can be altered in developmental basal ganglia disorders. [source] Zebrafish as a model for developmental neurotoxicity testing,,BIRTH DEFECTS RESEARCH, Issue 7 2006Christopher Ton Abstract BACKGROUND: To establish zebrafish as a developmental toxicity model, we used 7 well-characterized compounds to examine several parameters of neurotoxicity during development. METHODS: Embryos were exposed by semistatic immersion from 6 hrs postfertilization (hpf). Teratogenicity was assessed using a modified method previously developed by Phylonix. Dying cells in the brain were assessed by acridine orange staining (these cells are likely to be apoptotic). Motor neurons were assessed by antiacetylated tubulin staining and catecholaminergic neurons were visualized by antityrosine hydroxylase staining. RESULTS: Atrazine, dichlorodiphenyltrichloroethane (DDT), and 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) were primarily teratogenic and not specifically neurotoxic. 2,4-dichlorophenoxyacetic acid (2,4-D), dieldrin, and nonylphenol showed specific neurotoxicity; dieldrin and nonylphenol were specifically toxic to catecholaminergic neurons. Malathion, although not teratogenic, showed some nonspecific toxicity. CONCLUSIONS: Teratogenicity measured in 96-hpf zebrafish is predictive of mammalian teratogenicity and is useful in determining whether a compound causes specific neurotoxicity or general developmental toxicity. Induction of apoptosis or necrosis is an indicator of neurotoxicity. An effect on motor neurons in the caudal third of the embryo correlates with expected defects in motility. Overall, our results showed a strong correlation with mammalian data and suggest that zebrafish is a predictive animal model for neurotoxicity screening. Birth Defects Research (Part A) 76:553,567, 2006. Published 2006 Wiley-Liss, Inc. [source] | ||||||||||