Neurochemistry
Dysregulation of Intracellular Dopamine Stores Revealed in the R6/2 Mouse Striatum.
Publication Date: 2009 Nov 19 PMID: 19929911
Authors: Ortiz, A. N. - Kurth, B. J. - Osterhaus, G. L. - Johnson, M. A.
Journal: J Neurochem
Huntington's disease is a fatal, neurodegenerative movement disorder characterized by preferential and extensive striatal degeneration. Here, we used fast-scan cyclic voltammetry to study the mobilization and efflux of reserve pool dopamine in striatal brain slices from Huntington's disease model R6/2 mice. When applying stimulus trains of 120 pulses, evoked dopamine release in wild-type slices was greater than that in R6/2 slices at the higher frequencies (50 and 60 Hz). To quantify cytosolic and reserve pool dopamine levels, amphetamine-induced dopamine efflux was measured after pre-treatment with either tetrabenazine or alpha-methyl-p-tyrosine. Slices from 12-week old R6/2 mice released less dopamine than slices from wild-type mice, while no difference was noted in slices from 6-week old mice. The vesicular release of reserve pool dopamine, mobilized by treatment with cocaine, was shorter lived in R6/2 slices compared to wild-type slices even though peak dopamine release was the same. Moreover, the number of dopamine reserve pool vesicles in R6/2 mice was less than half of that in wild-type. Therefore, our data suggest that the same number of dopamine molecules are present in each reserve pool vesicle in WT and R6/2 mice and that these vesicles are readily mobilized in both genotypes; however, R6/2 mice have fewer dopamine reserve pool vesicles available for mobilization.
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Authors: Ortiz, A. N. - Kurth, B. J. - Osterhaus, G. L. - Johnson, M. A.
Journal: J Neurochem
Huntington's disease is a fatal, neurodegenerative movement disorder characterized by preferential and extensive striatal degeneration. Here, we used fast-scan cyclic voltammetry to study the mobilization and efflux of reserve pool dopamine in striatal brain slices from Huntington's disease model R6/2 mice. When applying stimulus trains of 120 pulses, evoked dopamine release in wild-type slices was greater than that in R6/2 slices at the higher frequencies (50 and 60 Hz). To quantify cytosolic and reserve pool dopamine levels, amphetamine-induced dopamine efflux was measured after pre-treatment with either tetrabenazine or alpha-methyl-p-tyrosine. Slices from 12-week old R6/2 mice released less dopamine than slices from wild-type mice, while no difference was noted in slices from 6-week old mice. The vesicular release of reserve pool dopamine, mobilized by treatment with cocaine, was shorter lived in R6/2 slices compared to wild-type slices even though peak dopamine release was the same. Moreover, the number of dopamine reserve pool vesicles in R6/2 mice was less than half of that in wild-type. Therefore, our data suggest that the same number of dopamine molecules are present in each reserve pool vesicle in WT and R6/2 mice and that these vesicles are readily mobilized in both genotypes; however, R6/2 mice have fewer dopamine reserve pool vesicles available for mobilization.
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STEM CELLS IN THE ADULT RAT SPINAL CORD: PLASTICITY AFTER INJURY AND TREADMILL TRAINING EXERCISE.
Publication Date: 2009 Nov 18 PMID: 19925583
Authors: Foret, A. - Quertainmont, R. - Botman, O. - Bouhy, D. - Amabili, P. - Brook, G. - Schoenen, J. - Franzen, R.
Journal: J Neurochem
ABSTRACT Ependymal cells located around the central canal of the adult spinal cord are considered as a source of neural stem cells (NSCs) and represent an interesting pool of endogenous stem cells for repair strategies. Physical exercise is known to increase ependymal cell proliferation, while improving functional recovery. In this work, we further characterized those endogenous NSCs within the normal and injured adult rat spinal cord and investigated the effects of treadmill training using immunohistochemical and behavioural studies. In uninjured untrained rats, Sox-2, a NSC marker, was detected in all ependymal cells of the central canal, and also scattered throughout the parenchyma of the spinal cord. Within the lesion, Sox-2 expression increased transiently, while the number of nestin-positive ependymal cells increased with a concomitant enhancement of proliferation, as indicated by the mitotic markers Ki67 and BrdU. Exercise, which improved functional recovery and autonomous micturition, maintained nestin expression in both injured and uninjured spinal cords, with a positive correlation between locomotor recovery and the number of nestin-positive cells.
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Authors: Foret, A. - Quertainmont, R. - Botman, O. - Bouhy, D. - Amabili, P. - Brook, G. - Schoenen, J. - Franzen, R.
Journal: J Neurochem
ABSTRACT Ependymal cells located around the central canal of the adult spinal cord are considered as a source of neural stem cells (NSCs) and represent an interesting pool of endogenous stem cells for repair strategies. Physical exercise is known to increase ependymal cell proliferation, while improving functional recovery. In this work, we further characterized those endogenous NSCs within the normal and injured adult rat spinal cord and investigated the effects of treadmill training using immunohistochemical and behavioural studies. In uninjured untrained rats, Sox-2, a NSC marker, was detected in all ependymal cells of the central canal, and also scattered throughout the parenchyma of the spinal cord. Within the lesion, Sox-2 expression increased transiently, while the number of nestin-positive ependymal cells increased with a concomitant enhancement of proliferation, as indicated by the mitotic markers Ki67 and BrdU. Exercise, which improved functional recovery and autonomous micturition, maintained nestin expression in both injured and uninjured spinal cords, with a positive correlation between locomotor recovery and the number of nestin-positive cells.
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Trichloroethylene Induces Dopaminergic Neurodegeneration in Fisher 344 Rats.
Publication Date: 2009 Nov 17 PMID: 19922440
Authors: Liu, M. - Choi, D. Y. - Hunter, R. L. - Pandya, J. D. - Cass, W. A. - Sullivan, P. G. - Kim, H. C. - Gash, D. M. - Bing, G.
Journal: J Neurochem
Trichloroethylene, a chlorinated solvent widely used as a degreasing agent, is a common environmental contaminant. Emerging evidence suggests that chronic exposure to trichloroethylene may contribute to the development of Parkinson's disease. The purpose of this study was to determine if selective loss of nigrostriatal dopaminergic neurons could be reproduced by systemic exposure of adult Fisher 344 rats to trichloroethylene. In our experiments, oral administration of trichloroethylene induced a significant loss of dopaminergic neurons in the substantia nigra pars compacta in a dose-dependent manner, whereas the number of both cholinergic and GABAergic neurons were not decreased in the striatum. There was a robust decline in striatal levels of 3, 4-dihydroxyphenylacetic acid without a significant depletion of striatal dopamine. Rats treated with trichloroethylene showed defects in rotarod behavior test. We also found a significantly reduced mitochondrial complex I activity with elevated oxidative stress markers and activated microglia in the nigral area. In addition, we observed intracellular alpha-synuclein accumulation in the dorsal motor nucleus of the vagus nerve, with some in nigral neurons, but little in neurons of cerebral cortex. Overall, our animal model exhibits some important features of Parkinsonism, and further supports that trichloroethylene may be an environmental risk factors for Parkinson's disease.
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Authors: Liu, M. - Choi, D. Y. - Hunter, R. L. - Pandya, J. D. - Cass, W. A. - Sullivan, P. G. - Kim, H. C. - Gash, D. M. - Bing, G.
Journal: J Neurochem
Trichloroethylene, a chlorinated solvent widely used as a degreasing agent, is a common environmental contaminant. Emerging evidence suggests that chronic exposure to trichloroethylene may contribute to the development of Parkinson's disease. The purpose of this study was to determine if selective loss of nigrostriatal dopaminergic neurons could be reproduced by systemic exposure of adult Fisher 344 rats to trichloroethylene. In our experiments, oral administration of trichloroethylene induced a significant loss of dopaminergic neurons in the substantia nigra pars compacta in a dose-dependent manner, whereas the number of both cholinergic and GABAergic neurons were not decreased in the striatum. There was a robust decline in striatal levels of 3, 4-dihydroxyphenylacetic acid without a significant depletion of striatal dopamine. Rats treated with trichloroethylene showed defects in rotarod behavior test. We also found a significantly reduced mitochondrial complex I activity with elevated oxidative stress markers and activated microglia in the nigral area. In addition, we observed intracellular alpha-synuclein accumulation in the dorsal motor nucleus of the vagus nerve, with some in nigral neurons, but little in neurons of cerebral cortex. Overall, our animal model exhibits some important features of Parkinsonism, and further supports that trichloroethylene may be an environmental risk factors for Parkinson's disease.
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Activation of Krox20 Gene Expression by Sox10 in Myelinating Schwann Cells.
Publication Date: 2009 Nov 17 PMID: 19922439
Authors: Reiprich, S. - Kriesch, J. - Schreiner, S. - Wegner, M.
Journal: J Neurochem
The HMG domain transcription factor Sox10 is believed to influence myelination in Schwann cells by directly activating myelin genes and by inducing Krox20 as a pivotal regulator of peripheral myelination. Krox20 induction at this stage is thought to be mediated by the myelinating Schwann cell element (MSE) 35 kilobases downstream of the Krox20 transcriptional start site and requires cooperation with Oct6. Here, we prove for the first time in vivo that Schwann cell-specific Krox20 expression indeed depends on Sox10. We also provide evidence that Sox10 functions through multiple, mostly monomeric binding sites in the MSE in a manner that should render the enhancer exquisitely sensitive to Sox10 levels. Synergistic activation of the enhancer by Sox10 and Oct6 furthermore does not involve cooperative binding to closely spaced binding sites in defined composite elements. Nevertheless, the POU domain of Oct6 and the HMG domain of Sox10 as the two DNA-binding domains were both essential indicating that each transcription factor has to bind independently to DNA. Whereas the POU domain was the only important region of Oct6, two further Sox10 domains were required for synergistic Krox20 activation. These were the carboxyterminal transactivation domain and the conserved K2 domain in the central portion of Sox10. All required regions are conserved in several closely related POU and Sox proteins thus explaining why Oct6 and Sox10 can be replaced by their relatives during Krox20 induction in myelinating Schwann cells.
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Authors: Reiprich, S. - Kriesch, J. - Schreiner, S. - Wegner, M.
Journal: J Neurochem
The HMG domain transcription factor Sox10 is believed to influence myelination in Schwann cells by directly activating myelin genes and by inducing Krox20 as a pivotal regulator of peripheral myelination. Krox20 induction at this stage is thought to be mediated by the myelinating Schwann cell element (MSE) 35 kilobases downstream of the Krox20 transcriptional start site and requires cooperation with Oct6. Here, we prove for the first time in vivo that Schwann cell-specific Krox20 expression indeed depends on Sox10. We also provide evidence that Sox10 functions through multiple, mostly monomeric binding sites in the MSE in a manner that should render the enhancer exquisitely sensitive to Sox10 levels. Synergistic activation of the enhancer by Sox10 and Oct6 furthermore does not involve cooperative binding to closely spaced binding sites in defined composite elements. Nevertheless, the POU domain of Oct6 and the HMG domain of Sox10 as the two DNA-binding domains were both essential indicating that each transcription factor has to bind independently to DNA. Whereas the POU domain was the only important region of Oct6, two further Sox10 domains were required for synergistic Krox20 activation. These were the carboxyterminal transactivation domain and the conserved K2 domain in the central portion of Sox10. All required regions are conserved in several closely related POU and Sox proteins thus explaining why Oct6 and Sox10 can be replaced by their relatives during Krox20 induction in myelinating Schwann cells.
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Diacylglycerol kinases in the regulation of dendritic spines.
Publication Date: 2009 Nov 17 PMID: 19922438
Authors: Kim, K. - Yang, J. - Kim, E.
Journal: J Neurochem
Diacylglycerol (DAG) is an important lipid signaling molecule that binds and activates various downstream effectors. Tight control over the production and removal of DAG is important in maintaining the dynamic responses of the DAG signaling system to a changing environment. Diacylglycerol kinases (DGKs) are enzymes that convert DAG to phosphatidic acid (PA). This conversion terminates DAG signaling and, at the same time, initiates additional signaling events downstream of PA, which also acts as a lipid signaling molecule. However, little is known about how (or if) DGKs are targeted to specific subcellular sites or how DGKs tightly regulate local DAG and PA signaling. Dendritic spines are tiny protrusions on neuronal dendrites that receive the majority of excitatory synaptic inputs. They are also the sites where DAG molecules are produced through activation of postsynaptic receptors, including metabotropic glutamate receptors and N-methyl-D-aspartate (NMDA) receptors. Accumulating evidence indicates that synaptic levels of DAG and PA are important determinants of dendritic spine stability and that the DGKzeta isoform at excitatory postsynaptic sites is critically involved in spine maintenance. In addition, DGKzeta appears to form a multi-protein complex with functionally related proteins to organize efficient DAG and PA signaling pathways at excitatory synapses.
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Authors: Kim, K. - Yang, J. - Kim, E.
Journal: J Neurochem
Diacylglycerol (DAG) is an important lipid signaling molecule that binds and activates various downstream effectors. Tight control over the production and removal of DAG is important in maintaining the dynamic responses of the DAG signaling system to a changing environment. Diacylglycerol kinases (DGKs) are enzymes that convert DAG to phosphatidic acid (PA). This conversion terminates DAG signaling and, at the same time, initiates additional signaling events downstream of PA, which also acts as a lipid signaling molecule. However, little is known about how (or if) DGKs are targeted to specific subcellular sites or how DGKs tightly regulate local DAG and PA signaling. Dendritic spines are tiny protrusions on neuronal dendrites that receive the majority of excitatory synaptic inputs. They are also the sites where DAG molecules are produced through activation of postsynaptic receptors, including metabotropic glutamate receptors and N-methyl-D-aspartate (NMDA) receptors. Accumulating evidence indicates that synaptic levels of DAG and PA are important determinants of dendritic spine stability and that the DGKzeta isoform at excitatory postsynaptic sites is critically involved in spine maintenance. In addition, DGKzeta appears to form a multi-protein complex with functionally related proteins to organize efficient DAG and PA signaling pathways at excitatory synapses.
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Differences in the C-terminus contribute to variations in trafficking between rat and human 5-HT(2A) receptor isoforms: Identification of a primate-specific tripeptide ASK motif that confers GRK-2 and beta arrestin-2 interactions.
Publication Date: 2009 Nov 16 PMID: 19919577
Authors: Bhattacharya, A. - Sankar, S. - Panicker, M. M.
Journal: J Neurochem
Internalization and recycling of GPCRs are important cellular processes regulating receptor function. These are receptor-subtype and cell type-specific. Though important, trafficking variations between receptor isoforms of different species has received limited attention. We report here, differences in internalization and recycling between rat and human serotonin 2A receptor (5-HT(2A)R) isoforms expressed in HEK 293 cells in response to serotonin. Although the human and rat 5-HT(2A) receptors differ by only a few amino acids, the human receptor takes longer to recycle to the cell surface after internalization, with the additional involvement of beta arrestin-2 and GRK-2. The interaction of beta arrestin-2 with the human receptor causes the delay in recycling and is dependent on a primate-specific ASK motif present in the C-terminus of the receptor. Conversion of this motif to NCT, the corresponding sequence present in the rat isoform, results in the human isoform trafficking like the rat receptor. Replacing the serine 457 with alanine in the ASK motif of human isoform resulted in faster recycling, though with continued arrestin-dependent internalization. This study establishes significant differences between the two isoforms with important implications in our understanding of the human 5-HT(2A)R functions; and indicates that extrapolating results from non-human receptor isoforms to human subtypes is not without caveats.
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Authors: Bhattacharya, A. - Sankar, S. - Panicker, M. M.
Journal: J Neurochem
Internalization and recycling of GPCRs are important cellular processes regulating receptor function. These are receptor-subtype and cell type-specific. Though important, trafficking variations between receptor isoforms of different species has received limited attention. We report here, differences in internalization and recycling between rat and human serotonin 2A receptor (5-HT(2A)R) isoforms expressed in HEK 293 cells in response to serotonin. Although the human and rat 5-HT(2A) receptors differ by only a few amino acids, the human receptor takes longer to recycle to the cell surface after internalization, with the additional involvement of beta arrestin-2 and GRK-2. The interaction of beta arrestin-2 with the human receptor causes the delay in recycling and is dependent on a primate-specific ASK motif present in the C-terminus of the receptor. Conversion of this motif to NCT, the corresponding sequence present in the rat isoform, results in the human isoform trafficking like the rat receptor. Replacing the serine 457 with alanine in the ASK motif of human isoform resulted in faster recycling, though with continued arrestin-dependent internalization. This study establishes significant differences between the two isoforms with important implications in our understanding of the human 5-HT(2A)R functions; and indicates that extrapolating results from non-human receptor isoforms to human subtypes is not without caveats.
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C1q enhances microglial clearance of apoptotic neurons and neuronal blebs, and modulates subsequent inflammatory cytokine production.
Publication Date: 2009 Nov 16 PMID: 19919576
Authors: Fraser, D. A. - Pisalyaput, K. - Tenner, A. J.
Journal: J Neurochem
The expression of C1q, a recognition molecule of the complement system, is upregulated following neuronal injury and is detected early in neurodegenerative disorders such as Alzheimer's disease. This multimeric protein triggers an enhancement of phagocytosis of suboptimally opsonized targets by microglia, the phagocytic cells of the CNS, similar to other phagocytes, enhances the uptake of apoptotic cells in peripheral phagocytes, and suppresses inflammatory cytokine production in human monocytes, macrophages and dendritic cells in the absence of activation of the entire complement cascade. The goal of this study was to determine if C1q could influence the inflammatory response to injury in the CNS, using primary rat microglia and neurons. The data show that microglia preferentially ingest apoptotic cells in comparison to live cells, like other professional phagocytes, that microglial ingestion of apoptotic neurons and neuronal blebs is enhanced by the presence of normal serum and that these enhanced levels of uptake are diminished in serum depleted of C1q. In addition, purified C1q bound to apoptotic neurons and neuronal blebs in a dose dependent manner, and alone triggered a significant enhancement of uptake by microglia. Microglia added to C1q coated wells or fed apoptotic neurons or neuronal blebs coated with C1q suppressed the LPS-induced production of proinflammatory cytokines IL-1alpha, IL-1beta, IL-6 and TNF-alpha, while the presence of C1q enhanced levels of the chemokine MCP-1/CCL2. The data are consistent with a protective role for C1q in the CNS during early stages of cell death by enhancing microglial clearance of apoptotic cells and suppressing proinflammatory cytokines.
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Authors: Fraser, D. A. - Pisalyaput, K. - Tenner, A. J.
Journal: J Neurochem
The expression of C1q, a recognition molecule of the complement system, is upregulated following neuronal injury and is detected early in neurodegenerative disorders such as Alzheimer's disease. This multimeric protein triggers an enhancement of phagocytosis of suboptimally opsonized targets by microglia, the phagocytic cells of the CNS, similar to other phagocytes, enhances the uptake of apoptotic cells in peripheral phagocytes, and suppresses inflammatory cytokine production in human monocytes, macrophages and dendritic cells in the absence of activation of the entire complement cascade. The goal of this study was to determine if C1q could influence the inflammatory response to injury in the CNS, using primary rat microglia and neurons. The data show that microglia preferentially ingest apoptotic cells in comparison to live cells, like other professional phagocytes, that microglial ingestion of apoptotic neurons and neuronal blebs is enhanced by the presence of normal serum and that these enhanced levels of uptake are diminished in serum depleted of C1q. In addition, purified C1q bound to apoptotic neurons and neuronal blebs in a dose dependent manner, and alone triggered a significant enhancement of uptake by microglia. Microglia added to C1q coated wells or fed apoptotic neurons or neuronal blebs coated with C1q suppressed the LPS-induced production of proinflammatory cytokines IL-1alpha, IL-1beta, IL-6 and TNF-alpha, while the presence of C1q enhanced levels of the chemokine MCP-1/CCL2. The data are consistent with a protective role for C1q in the CNS during early stages of cell death by enhancing microglial clearance of apoptotic cells and suppressing proinflammatory cytokines.
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Expression of CXCL10 in cultured cortical neurons.
Publication Date: 2009 Nov 16 PMID: 19919575
Authors: Vinet, J. - de Jong, E. K. - Boddeke, H. W. - Stanulovic, V. - Brouwer, N. - Granic, I. - Eisel, U. L. - Liem, R. S. - Biber, K.
Journal: J Neurochem
Chemokines expressed in neurons are important mediators in neuron-neuron and neuron-glia signaling. One of these chemokines is CCL21 that activates microglia via the chemokine receptor CXCR3. Since neurons also express CXCL10, a main ligand for CXCR3, we have thus investigated in detail the expression pattern of CXCL10 in neurons. We show that CXCL10 is constitutively expressed by neurons, is stored in large dense-core vesicles and is not regulated by neuronal injury or stress. Neuronal CXCL10 release occurred constitutively at low level. In vivo CXCL10 expression was found in the developing brain at various embryonic stages and its peak expression correlates with the presence of CD11b- and GFAP-positive cells expressing CXCR3. These results suggest a possible role of neuronal CXCL10 in recruitment and homing of glial cells during embryogenesis.
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Authors: Vinet, J. - de Jong, E. K. - Boddeke, H. W. - Stanulovic, V. - Brouwer, N. - Granic, I. - Eisel, U. L. - Liem, R. S. - Biber, K.
Journal: J Neurochem
Chemokines expressed in neurons are important mediators in neuron-neuron and neuron-glia signaling. One of these chemokines is CCL21 that activates microglia via the chemokine receptor CXCR3. Since neurons also express CXCL10, a main ligand for CXCR3, we have thus investigated in detail the expression pattern of CXCL10 in neurons. We show that CXCL10 is constitutively expressed by neurons, is stored in large dense-core vesicles and is not regulated by neuronal injury or stress. Neuronal CXCL10 release occurred constitutively at low level. In vivo CXCL10 expression was found in the developing brain at various embryonic stages and its peak expression correlates with the presence of CD11b- and GFAP-positive cells expressing CXCR3. These results suggest a possible role of neuronal CXCL10 in recruitment and homing of glial cells during embryogenesis.
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Hypoxia Protects Neuronal Cells from Human Prion Protein fragment-induced Apoptosis.
Publication Date: 2009 Nov 16 PMID: 19919574
Authors: Seo, J. S. - Seol, J. W. - Moon, M. H. - Jeong, J. K. - Lee, Y. J. - Park, S. Y.
Journal: J Neurochem
Prion diseases are neurodegenerative disorders characterized by the accumulation of an abnormal isoform of the prion protein PrP(Sc). Human prion protein (HuPrP) fragment, PrP (106-126), may contain most of the pathological features associated with PrP(Sc). Hypoxic conditions elicit cellular responses adaptively designed to improve cell survival and have an important role in the process of cell survival. We investigate the effects of hypoxia on PrP (106-126)-induced apoptosis in the present study. Human neuroblastoma and glioblastoma cells were incubated with varied doses of PrP (106-126) under both normoxic or hypoxic conditions, in order to determine the regulatory effects of hypoxia on PrP (106-126)-induced apoptosis. The results indicate that hypoxia protects neuronal cells against PrP (106-126)-induced cell death by activating the Akt signal, which is inactivated by prion proteins, and inhibiting PrP (106-126)-induced caspase-3 activation. Low oxygen conditions increase the Bcl-2 protein, which is associated with anti-apoptotic signals, and recover the PrP (106-126)-induced reduction in mitochondrial transmembrane potential (MTP). This study demonstrates that hypoxia inhibits PrP (106-126)-induced neuron cell death by regulating Akt and Akt-related signaling, and it also suggests that prion-related neuronal damage and disease may be regulated by hypoxia or by hypoxic-inducing genes.
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Authors: Seo, J. S. - Seol, J. W. - Moon, M. H. - Jeong, J. K. - Lee, Y. J. - Park, S. Y.
Journal: J Neurochem
Prion diseases are neurodegenerative disorders characterized by the accumulation of an abnormal isoform of the prion protein PrP(Sc). Human prion protein (HuPrP) fragment, PrP (106-126), may contain most of the pathological features associated with PrP(Sc). Hypoxic conditions elicit cellular responses adaptively designed to improve cell survival and have an important role in the process of cell survival. We investigate the effects of hypoxia on PrP (106-126)-induced apoptosis in the present study. Human neuroblastoma and glioblastoma cells were incubated with varied doses of PrP (106-126) under both normoxic or hypoxic conditions, in order to determine the regulatory effects of hypoxia on PrP (106-126)-induced apoptosis. The results indicate that hypoxia protects neuronal cells against PrP (106-126)-induced cell death by activating the Akt signal, which is inactivated by prion proteins, and inhibiting PrP (106-126)-induced caspase-3 activation. Low oxygen conditions increase the Bcl-2 protein, which is associated with anti-apoptotic signals, and recover the PrP (106-126)-induced reduction in mitochondrial transmembrane potential (MTP). This study demonstrates that hypoxia inhibits PrP (106-126)-induced neuron cell death by regulating Akt and Akt-related signaling, and it also suggests that prion-related neuronal damage and disease may be regulated by hypoxia or by hypoxic-inducing genes.
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Studies on the Immune Response and Preparation of Antibodies Against a Large Panel of Conjugated Neurotransmitters and Biogenic Amines-Specific Polyclonal Antibody response and Tolerance-
Publication Date: 2009 Nov 13 PMID: 19912471
Authors: Huisman, H. - Wynveen, P. - Setter, P. W.
Journal: J Neurochem
We described the production and characterization of antibodies against three important groups of neuro-active haptens e.g. neurotransmitters and biogenic amines. Firstly, from the Tryptophane metabolic pathway: Tryptamine, Serotonin, 5-hydroxy-indole acetic acid and Melatonin. Secondly, the Tyrosine metabolic pathway: Tyramine, Dopamine, Dihydroxyphenyl acetic acid and Norepinephrine. Thirdly, antibodies against excitatory - and inhibitory neurotransmitters: Glycine, Glutamate, Glutamine and GABA. Immunogenic conjugates were prepared after linking haptens to carrier proteins. Most antibodies displayed high specificity against corresponding neuro-active haptens conjugated in vitro and in situ in biological specimens, but not to closely related conjugated metabolites, precursors, pharmaceuticals, agonists, antagonists, or free neuro-active haptens. Conjugated Nor-epinephrine was highly tolerant in different animal species and produced incidentally a short specific antibody response.
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Authors: Huisman, H. - Wynveen, P. - Setter, P. W.
Journal: J Neurochem
We described the production and characterization of antibodies against three important groups of neuro-active haptens e.g. neurotransmitters and biogenic amines. Firstly, from the Tryptophane metabolic pathway: Tryptamine, Serotonin, 5-hydroxy-indole acetic acid and Melatonin. Secondly, the Tyrosine metabolic pathway: Tyramine, Dopamine, Dihydroxyphenyl acetic acid and Norepinephrine. Thirdly, antibodies against excitatory - and inhibitory neurotransmitters: Glycine, Glutamate, Glutamine and GABA. Immunogenic conjugates were prepared after linking haptens to carrier proteins. Most antibodies displayed high specificity against corresponding neuro-active haptens conjugated in vitro and in situ in biological specimens, but not to closely related conjugated metabolites, precursors, pharmaceuticals, agonists, antagonists, or free neuro-active haptens. Conjugated Nor-epinephrine was highly tolerant in different animal species and produced incidentally a short specific antibody response.
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From Wikipedia,
Neurochemistry is the specific study of neurochemicals, which include neurotransmitters and other molecules such as neuro-active drugs that influence neuron function. This principle closely examines the manner in which these neurochemicals influence the network of neural operation. This evolving area of neuroscience offers a neurochemist a micro-macro connection between the analysis of organic compounds active in the nervous system and neural processes such as cortical plasticity, neurogenesis and neural differentiation.
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