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Thomas C Wessel - One of the best experts on this subject based on the ideXlab platform.
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differential in vivo regulation of mrna encoding the norepinephrine transporter and tyrosine hydroxylase in rat adrenal medulla and Locus Ceruleus
Journal of Neurochemistry, 2002Co-Authors: Joseph F Cubells, Harriet Baker, Bruce T Volpe, Youngin Chung, Thomas A Houpt, Thomas C WesselAbstract:: To investigate the regulation of norepinephrine transporter mRNA in vivo, we analyzed the effects of reserpine on its expression in the rat adrenal medulla and Locus Ceruleus. First, PCR was used to clone a 0.5-kb rat cDNA fragment that exhibits 87% nucleotide identity to the corresponding human norepinephrine transporter cDNA sequence. In situ, the cDNA hybridizes specifically within norepinephrine-secreting cells, but in neither dopamine nor serotonin neurons, suggesting strongly it is a partial rat norepinephrine transporter cDNA. Reserpine, 10 mg/kg administered 24 h premortem, decreased steady-state levels of norepinephrine transporter mRNA in the adrenal medulla by ∼65% and in the Locus Ceruleus by ∼25%, as determined by quantitative in situ hybridization. Northern analysis confirmed the results of the in situ hybridization analysis in the adrenal medulla but did not detect the smaller changes observed in the Locus Ceruleus. Both analyses showed that reserpine increased tyrosine hydroxylase expression in the adrenal medulla and Locus Ceruleus. These results suggest that noradrenergic neurons and adrenal chromaffin cells can coordinate opposing changes in systems mediating catecholamine uptake and synthesis, to compensate for catecholamine depletion.
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Differential In Vivo Regulation of mRNA Encoding the Norepinephrine Transporter and Tyrosine Hydroxylase in Rat Adrenal Medulla and Locus Ceruleus
Journal of neurochemistry, 2002Co-Authors: Joseph F Cubells, Harriet Baker, Bruce T Volpe, Youngin Chung, Thomas A Houpt, Thomas C Wessel, Kwang-soo Kim, Tong H. JohAbstract:To investigate the regulation of norepinephrine transporter mRNA in vivo, we analyzed the effects of reserpine on its expression in the rat adrenal medulla and Locus Ceruleus. First, PCR was used to clone a 0.5-kb rat cDNA fragment that exhibits 87% nucleotide identity to the corresponding human norepinephrine transporter cDNA sequence. In situ, the cDNA hybridizes specifically within norepinephrine-secreting cells, but in neither dopamine nor serotonin neurons, suggesting strongly it is a partial rat norepinephrine transporter cDNA. Reserpine, 10 mg/kg administered 24 h premortem, decreased steady-state levels of norepinephrine transporter mRNA in the adrenal medulla by approximately 65% and in the Locus Ceruleus by approximately 25%, as determined by quantitative in situ hybridization. Northern analysis confirmed the results of the in situ hybridization analysis in the adrenal medulla but did not detect the smaller changes observed in the Locus Ceruleus. Both analyses showed that reserpine increased tyrosine hydroxylase expression in the adrenal medulla and Locus Ceruleus. These results suggest that noradrenergic neurons and adrenal chromaffin cells can coordinate opposing changes in systems mediating catecholamine uptake and synthesis, to compensate for catecholamine depletion.
Joseph F Cubells - One of the best experts on this subject based on the ideXlab platform.
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differential in vivo regulation of mrna encoding the norepinephrine transporter and tyrosine hydroxylase in rat adrenal medulla and Locus Ceruleus
Journal of Neurochemistry, 2002Co-Authors: Joseph F Cubells, Harriet Baker, Bruce T Volpe, Youngin Chung, Thomas A Houpt, Thomas C WesselAbstract:: To investigate the regulation of norepinephrine transporter mRNA in vivo, we analyzed the effects of reserpine on its expression in the rat adrenal medulla and Locus Ceruleus. First, PCR was used to clone a 0.5-kb rat cDNA fragment that exhibits 87% nucleotide identity to the corresponding human norepinephrine transporter cDNA sequence. In situ, the cDNA hybridizes specifically within norepinephrine-secreting cells, but in neither dopamine nor serotonin neurons, suggesting strongly it is a partial rat norepinephrine transporter cDNA. Reserpine, 10 mg/kg administered 24 h premortem, decreased steady-state levels of norepinephrine transporter mRNA in the adrenal medulla by ∼65% and in the Locus Ceruleus by ∼25%, as determined by quantitative in situ hybridization. Northern analysis confirmed the results of the in situ hybridization analysis in the adrenal medulla but did not detect the smaller changes observed in the Locus Ceruleus. Both analyses showed that reserpine increased tyrosine hydroxylase expression in the adrenal medulla and Locus Ceruleus. These results suggest that noradrenergic neurons and adrenal chromaffin cells can coordinate opposing changes in systems mediating catecholamine uptake and synthesis, to compensate for catecholamine depletion.
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Differential In Vivo Regulation of mRNA Encoding the Norepinephrine Transporter and Tyrosine Hydroxylase in Rat Adrenal Medulla and Locus Ceruleus
Journal of neurochemistry, 2002Co-Authors: Joseph F Cubells, Harriet Baker, Bruce T Volpe, Youngin Chung, Thomas A Houpt, Thomas C Wessel, Kwang-soo Kim, Tong H. JohAbstract:To investigate the regulation of norepinephrine transporter mRNA in vivo, we analyzed the effects of reserpine on its expression in the rat adrenal medulla and Locus Ceruleus. First, PCR was used to clone a 0.5-kb rat cDNA fragment that exhibits 87% nucleotide identity to the corresponding human norepinephrine transporter cDNA sequence. In situ, the cDNA hybridizes specifically within norepinephrine-secreting cells, but in neither dopamine nor serotonin neurons, suggesting strongly it is a partial rat norepinephrine transporter cDNA. Reserpine, 10 mg/kg administered 24 h premortem, decreased steady-state levels of norepinephrine transporter mRNA in the adrenal medulla by approximately 65% and in the Locus Ceruleus by approximately 25%, as determined by quantitative in situ hybridization. Northern analysis confirmed the results of the in situ hybridization analysis in the adrenal medulla but did not detect the smaller changes observed in the Locus Ceruleus. Both analyses showed that reserpine increased tyrosine hydroxylase expression in the adrenal medulla and Locus Ceruleus. These results suggest that noradrenergic neurons and adrenal chromaffin cells can coordinate opposing changes in systems mediating catecholamine uptake and synthesis, to compensate for catecholamine depletion.
Roger Pamphlett - One of the best experts on this subject based on the ideXlab platform.
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Concentrations of toxic metals and essential trace elements vary among individual neurons in the human Locus Ceruleus.
PloS one, 2020Co-Authors: Roger Pamphlett, Stephen Kum Jew, Rachel Mak, Joonsup Lee, Michael E. Buckland, Antony J. Harding, David J. Paterson, Michael W. M. Jones, Peter A. LayAbstract:Objective Damage to Locus Ceruleus neurons could play a part in the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis because of impairment of the blood-brain barrier and enhanced neuroinflammation. The Locus Ceruleus has connections throughout the brain and spinal cord, so the characteristic widespread multifocal pathology in these disorders could be due to damage to different subsets of Locus Ceruleus neurons. Previous studies have shown that only certain Locus Ceruleus neurons accumulate the neurotoxic metal mercury. To find out if concentrations of other toxic metals or of essential trace elements also vary between individual Locus Ceruleus neurons, we used synchrotron X-ray fluorescence microscopy on frozen sections of Locus Ceruleus neurons taken from people with multiple sclerosis, in whom the Locus Ceruleus is structurally intact. Materials and methods Paraffin embedded sections containing the Locus Ceruleus from seven people with multiple sclerosis were stained with autometallography that demonstrates accumulations of mercury, silver and bismuth. These were compared to maps of multiple elements obtained from frozen sections of Locus Ceruleus neurons from the same people using X-ray fluorescence microscopy. Neurons in the anterior pons from three of these donors were used as internal controls. Results Autometallography staining was observed in scattered Locus Ceruleus neurons from three of the seven donors. X-ray fluorescence microscopy showed variations among individual Locus Ceruleus neurons in levels of mercury, selenium, iron, copper, lead, bromine, and rubidium. Variations between donors of Locus Ceruleus neuronal average levels of mercury, iron, copper, and bromine were also detected. Anterior pons neurons contained no mercury, had varied levels of iron, and had lower copper levels than Locus Ceruleus neurons. Conclusions Individual human Locus Ceruleus neurons contain varying levels of toxic metals and essential trace elements. In contrast, most toxic metals are absent or at low levels in nearby anterior pons neurons. The Locus Ceruleus plays a role in numerous central nervous system functions, including maintaining the blood-brain-barrier and limiting neuroinflammation. Toxic metals, or alterations in essential trace metals within individual Locus Ceruleus neurons, could be one factor determining the non-random destruction of Locus Ceruleus neurons in normal aging and neurodegenerative diseases, and subsequently the sites of the widespread multifocal central nervous system pathology in these disorders.
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Age-related accumulation of toxic metals in the human Locus Ceruleus.
PloS one, 2018Co-Authors: Roger Pamphlett, David P. Bishop, Stephen Kum Jew, Philip DobleAbstract:Damage to the Locus Ceruleus has been implicated in the pathogenesis of a number of neurological conditions. Locus Ceruleus neurons accumulate toxic metals such as mercury selectively, however, the presence of toxic metals in Locus Ceruleus neurons of people of different ages, and with a variety of disorders, is not known. To demonstrate at what age toxic metals are first detectable in the Locus Ceruleus, and to evaluate whether their presence is more common in certain clinicopathological conditions, we looked for these metals in 228 Locus Ceruleus samples. Samples were taken at coronial autopsies from individuals with a wide range of ages, pre-existing conditions and causes of death. Paraffin sections of pons containing the Locus Ceruleus were stained with silver nitrate autometallography, which indicates inorganic mercury, silver and bismuth within cells (termed autometallography-detected toxic metals, or AMG™). No Locus Ceruleus AMG neurons were seen in 38 individuals aged under 20 years. 47% of the 190 adults (ie, aged 20 years and over) had AMG Locus Ceruleus neurons. The proportion of adults with Locus Ceruleus AMG neurons increased during aging, except for a decreased proportion in the 90-plus years age group. No differences were found in the proportions of Locus Ceruleus AMG neurons between groups with different neurological, psychiatric, or other clinicopathological conditions, or among various causes of death. Elemental analysis with laser ablation-inductively coupled plasma-mass spectrometry was used to cross-validate the metals detected by AMG, by looking for silver, gold, bismuth, cadmium, chromium, iron, mercury, nickel, and lead in the Locus Ceruleus of ten individuals. This confirmed the presence of mercury in Locus Ceruleus samples containing AMG neurons, and showed cadmium, silver, lead, iron, and nickel in the Locus Ceruleus of some individuals. In conclusion, toxic metals stained by AMG (most likely inorganic mercury) appear in Locus Ceruleus neurons in early adult life. About half of adults in this study had Locus Ceruleus neurons containing inorganic mercury, and elemental analysis found a range of other toxic metals in the Locus Ceruleus. Locus Ceruleus inorganic mercury increased during aging, except for a decrease in advanced age, but was not found more often in any single clinicopathological condition or cause of death.
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Inorganic mercury in human astrocytes, oligodendrocytes, corticomotoneurons and the Locus Ceruleus: implications for multiple sclerosis, neurodegenerative disorders and gliomas.
Biometals : an international journal on the role of metal ions in biology biochemistry and medicine, 2018Co-Authors: Roger Pamphlett, Stephen Kum JewAbstract:Neurotoxic metals have been implicated in the pathogenesis of multiple sclerosis, neurodegenerative disorders and brain tumours but studies of the location of heavy metals in human brains are rare. In a man who injected himself with metallic mercury the cellular location of mercury in his brain was studied after 5 months of continuous exposure to inorganic mercury arising from metallic mercury deposits in his organs. Paraffin sections from the primary motor and sensory cortices and the Locus Ceruleus in the pons were stained with autometallography to detect inorganic mercury and combined with glial fibrillary acidic protein immunohistochemistry to identify astrocytes. Inorganic mercury was found in grey matter subpial, interlaminar, protoplasmic and varicose astrocytes, white matter fibrous astrocytes, grey but not white matter oligodendrocytes, corticomotoneurons and some Locus Ceruleus neurons. In summary, inorganic mercury is taken up by five types of human brain astrocytes, as well as by cortical oligodendrocytes, corticomotoneurons and Locus Ceruleus neurons. Mercury can induce oxidative stress, stimulate autoimmunity and damage DNA, mitochondria and lipid membranes, so its location in these CNS cells suggests it could play a role in the pathogenesis of multiple sclerosis, neurodegenerative conditions such as Alzheimer’s disease and amyotrophic lateral sclerosis, and glial tumours.
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Grades of AMG in the Locus Ceruleus.
2018Co-Authors: Roger Pamphlett, David P. Bishop, Stephen Kum Jew, Philip A. DobleAbstract:(A) Grade 0. No black AMG grains are seen in these Locus Ceruleus neurons that contain yellow-brown cytoplasmic neuromelanin granules. (B) Grade I. One (ie, fewer than 10%) of these Locus Ceruleus neurons (closed arrow) contains AMG. Free and macrophage-bound neuromelanin pigment (without AMG, open arrow) is seen in the neuropil. (C) Grade II. Two Locus Ceruleus neurons (arrows, 10–50%) stain with AMG. (D) Grade III. More than 50% of Locus Ceruleus AMG neurons are present. The intensity of staining varies between neurons, with a heavily-stained neuron (closed arrow) adjacent to a non-stained neuron (open arrow). AMG is also present in scattered free and macrophage-bound neuromelanin. All figures AMG/hematoxylin, Bars = 20 μm.
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Normal appearance and pathology of the Locus Ceruleus.
2018Co-Authors: Roger Pamphlett, David P. Bishop, Stephen Kum Jew, Philip A. DobleAbstract:(A) The Locus Ceruleus (LC, outlined) contains numerous, mostly neuromelanin-containing, neuronal cell bodies. White matter (WM) is present at the right, and the central grey of the pons (CGP) at the left. A large thin-walled blood vessel (closed arrow), probably a post-capillary venule, is seen within the Locus Ceruleus. A mesencephalic trigeminal neuron is seen in the upper right corner (open arrow). Hematoxylin and eosin, Bar = 100 μm. (B) The capillary density in the Locus Ceruleus is slightly increased, compared to adjacent white matter (WM), as seen by the red-immunostained capillary endothelial cells (some asterisked). Black AMG grains are present in several Locus Ceruleus neurons (one with arrow). AMG/hematoxylin/CD31, Bar = 50 μm. (C) This Locus Ceruleus has a reduced density of neurons. Free and macrophage-bound neuromelanin originating from destroyed Locus Ceruleus neurons is prominent, with this pigment having either AMG (closed arrow) or no AMG (open arrow). Some remaining Locus Ceruleus neurons either with (asterisks) or without AMG are seen. AMG/hematoxylin, Bar = 20 μm.
Tong H. Joh - One of the best experts on this subject based on the ideXlab platform.
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Differential In Vivo Regulation of mRNA Encoding the Norepinephrine Transporter and Tyrosine Hydroxylase in Rat Adrenal Medulla and Locus Ceruleus
Journal of neurochemistry, 2002Co-Authors: Joseph F Cubells, Harriet Baker, Bruce T Volpe, Youngin Chung, Thomas A Houpt, Thomas C Wessel, Kwang-soo Kim, Tong H. JohAbstract:To investigate the regulation of norepinephrine transporter mRNA in vivo, we analyzed the effects of reserpine on its expression in the rat adrenal medulla and Locus Ceruleus. First, PCR was used to clone a 0.5-kb rat cDNA fragment that exhibits 87% nucleotide identity to the corresponding human norepinephrine transporter cDNA sequence. In situ, the cDNA hybridizes specifically within norepinephrine-secreting cells, but in neither dopamine nor serotonin neurons, suggesting strongly it is a partial rat norepinephrine transporter cDNA. Reserpine, 10 mg/kg administered 24 h premortem, decreased steady-state levels of norepinephrine transporter mRNA in the adrenal medulla by approximately 65% and in the Locus Ceruleus by approximately 25%, as determined by quantitative in situ hybridization. Northern analysis confirmed the results of the in situ hybridization analysis in the adrenal medulla but did not detect the smaller changes observed in the Locus Ceruleus. Both analyses showed that reserpine increased tyrosine hydroxylase expression in the adrenal medulla and Locus Ceruleus. These results suggest that noradrenergic neurons and adrenal chromaffin cells can coordinate opposing changes in systems mediating catecholamine uptake and synthesis, to compensate for catecholamine depletion.
Bruce T Volpe - One of the best experts on this subject based on the ideXlab platform.
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differential in vivo regulation of mrna encoding the norepinephrine transporter and tyrosine hydroxylase in rat adrenal medulla and Locus Ceruleus
Journal of Neurochemistry, 2002Co-Authors: Joseph F Cubells, Harriet Baker, Bruce T Volpe, Youngin Chung, Thomas A Houpt, Thomas C WesselAbstract:: To investigate the regulation of norepinephrine transporter mRNA in vivo, we analyzed the effects of reserpine on its expression in the rat adrenal medulla and Locus Ceruleus. First, PCR was used to clone a 0.5-kb rat cDNA fragment that exhibits 87% nucleotide identity to the corresponding human norepinephrine transporter cDNA sequence. In situ, the cDNA hybridizes specifically within norepinephrine-secreting cells, but in neither dopamine nor serotonin neurons, suggesting strongly it is a partial rat norepinephrine transporter cDNA. Reserpine, 10 mg/kg administered 24 h premortem, decreased steady-state levels of norepinephrine transporter mRNA in the adrenal medulla by ∼65% and in the Locus Ceruleus by ∼25%, as determined by quantitative in situ hybridization. Northern analysis confirmed the results of the in situ hybridization analysis in the adrenal medulla but did not detect the smaller changes observed in the Locus Ceruleus. Both analyses showed that reserpine increased tyrosine hydroxylase expression in the adrenal medulla and Locus Ceruleus. These results suggest that noradrenergic neurons and adrenal chromaffin cells can coordinate opposing changes in systems mediating catecholamine uptake and synthesis, to compensate for catecholamine depletion.
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Differential In Vivo Regulation of mRNA Encoding the Norepinephrine Transporter and Tyrosine Hydroxylase in Rat Adrenal Medulla and Locus Ceruleus
Journal of neurochemistry, 2002Co-Authors: Joseph F Cubells, Harriet Baker, Bruce T Volpe, Youngin Chung, Thomas A Houpt, Thomas C Wessel, Kwang-soo Kim, Tong H. JohAbstract:To investigate the regulation of norepinephrine transporter mRNA in vivo, we analyzed the effects of reserpine on its expression in the rat adrenal medulla and Locus Ceruleus. First, PCR was used to clone a 0.5-kb rat cDNA fragment that exhibits 87% nucleotide identity to the corresponding human norepinephrine transporter cDNA sequence. In situ, the cDNA hybridizes specifically within norepinephrine-secreting cells, but in neither dopamine nor serotonin neurons, suggesting strongly it is a partial rat norepinephrine transporter cDNA. Reserpine, 10 mg/kg administered 24 h premortem, decreased steady-state levels of norepinephrine transporter mRNA in the adrenal medulla by approximately 65% and in the Locus Ceruleus by approximately 25%, as determined by quantitative in situ hybridization. Northern analysis confirmed the results of the in situ hybridization analysis in the adrenal medulla but did not detect the smaller changes observed in the Locus Ceruleus. Both analyses showed that reserpine increased tyrosine hydroxylase expression in the adrenal medulla and Locus Ceruleus. These results suggest that noradrenergic neurons and adrenal chromaffin cells can coordinate opposing changes in systems mediating catecholamine uptake and synthesis, to compensate for catecholamine depletion.
