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John P. Quinn - One of the best experts on this subject based on the ideXlab platform.
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an intronic domain within the rat Preprotachykinin a gene containing a ccct repetitive motif acts as an enhancer in differentiating embryonic stem cells
Neuroscience Letters, 1999Co-Authors: C. E. Fiskerstrand, E Lovejoy, Lesley Gerrard, John P. QuinnAbstract:Previous attempts by several groups to clone fragments containing intron 2 of the rat Preprotachykinin-A gene have generated deletions of various sizes. We have determined that these deletions occur within a specific region of the intron spanning a CCCT tandem repeat domain. We show that this intronic domain is able to support reporter gene expression in mouse embryonic stem (ES) cells that have been induced to differentiate but not in undifferentiated ES cells. No significant expression was observed in the HeLa clonal cell line. This demonstrates that this intron 2 domain is a highly restrictive enhancer and may be associated with differentiation.
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Neuronal-specific and nerve growth factor-inducible expression directed by the Preprotachykinin-A promoter delivered by an adeno-associated virus vector
Neuroscience, 1999Co-Authors: Patrick T. Harrison, Robert G. Dalziel, N.a. Ditchfield, John P. QuinnAbstract:The ability to manipulate the expression of genes within neurons provides unique opportunities to study the role of individual gene products in nervous system function. Virus vectors are a potentially rapid tool for the experimental manipulation of gene expression in the mammalian nervous system. However, a block to the use of virus vector systems in neurobiology is often the lack of cell-specific expression of the gene within the nervous system, and the immune and inflammatory responses to both the virus vector and the delivered gene. We have generated an adeno-associated virus vector that exploits the restricted expression pattern of the rat Preprotachykinin-A promoter to support reporter gene expression. We demonstrate that this virus has a neuronal-specific expression pattern. Moreover, it is shown for the first time that the proximal rat Preprotachykinin-A promoter is nerve growth factor inducible. This virus will be a useful tool to (i) modify neuronal phenotype by expressing therapeutic molecules or antisense nucleic acid and (ii) dissect the signal transduction pathways that regulate promoter function in vivo.
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A role for the octamer-binding protein in Preprotachykinin-a gene expression
Neuropeptides, 1998Co-Authors: S.c. Mendelson, C. E. Fiskerstrand, John P. QuinnAbstract:A rat Preprotachykinin-A promoter fragment has been previously identified which supports reporter gene activity in primary cultures of adult dorsal root ganglion neurons. That study demonstrated that two promoter domains which exhibit enhancer activity in these neurons are bound by the same classes of transcription factors. Further, the two domains exhibit similarities with respect to the relationship of bound transcription factors within each domain. This suggests that these domains may function in an identical manner or may act synergistically to regulate gene expression. These domains contain recognition motifs for at least three classes of transcription factors: octamer-binding proteins, Sp1-related proteins and an as yet unidentified but distinct factor. The definition of an octamer-binding protein site within these domains is of interest, as this class of factor has recently been suggested as mediating the effect of nerve growth factor in sensory neurons. Nerve growth factor is a well-characterized regulator of Preprotachykinin-A gene expression. Definition of these sites within the promoter allows for the design of rational experiments to address the mechanism of transcriptional regulation of the rat Preprotachykinin-A gene.
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The molecular biology of Preprotachykinin-A gene expression
Neuropeptides, 1996Co-Authors: C. E. Fiskerstrand, John P. QuinnAbstract:The expression of neuropeptides is largely tissue-specific and under strictly regulated and complex control. In view of the diversity of neuronal phenotypes, with concomitant plasticity of gene expression within any phenotype, it is obvious that there is coordinated activation and repression of genes. One of the central observations from these studies is that neuropeptide gene expression is dependent upon the combinatorial interaction of multiple transcription factors with the regulatory elements which determine mRNA synthesis. These factors mediate both tissue specific and stimulus inducible gene expression. We will illustrate some of the mechanisms that regulate neuropeptide gene expression utilizing our own studies on the rat Preprotachykinin-A gene (rPPT) and, where appropriate, expand on the generality of these findings to other neuropeptide genes.
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Repression of Preprotachykinin-A promoter activity is mediated by a proximal promoter element
Neuroscience, 1995Co-Authors: S.c. Mendelson, C.f. Morrison, J. Mcallister, J.m. Paterson, S.p. Dobson, P.k. Mulderry, John P. QuinnAbstract:Abstract The rat Preprotachykinin-A promoter, which is able to direct reporter gene expression in adult dorsal root ganglia neurons grown in culture, has no detectable activity in HeLa and PC12 cells. DNAase 1 footprinting and electrophoretic mobility shift analyses with HeLa nuclear extract indicated the presence of a protein complex binding to a region of the rat preprotachykinn-A gene promoter between the TATA ☐ and the major transcriptional start site. We demonstrate that the sequence of the Preprotachykinin-A promoter spanning nucleotides −47 to +92 functions to repress reporter gene expression in HeLa and PC12 cells but not in adult rat dorsal root ganglia grown in culture, and that this repression is correlated with a protein(s) binding to the element between the TATA ☐ and major transcription initiation site. These results indicate that the tissue-specific expression of the Preprotachykinin-A gene could require the interaction of both positive and negative regulatory DNA elements.
Nils Lindefors - One of the best experts on this subject based on the ideXlab platform.
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Decreased levels of Preprotachykinin-A and tachykinin NK1 receptor mRNA in specific regions of the rat striatum after electroconvulsive stimuli
European Journal of Pharmacology, 1997Co-Authors: O Zachrisson, A A Mathé, Nils LindeforsAbstract:The effects of electroconvulsive stimuli on the expression of mRNAs coding for Preprotachykinin-A and the substance P-sensitive tachykinin NK1 receptor were examined in subregions of the rat striatum. In the electroconvulsive stimuli-treated animals, a 43% decrease in Preprotachykinin-A mRNA was detected in the dorso-lateral caudate-putamen as compared to sham electroconvulsive stimuli treated animals. A 75% decrease in numerical density of tachykinin NK1 receptor mRNA positive neurons was found in the caudal part of the nucleus accumbens core. These findings provide new evidence for selective effects of electroconvulsive stimuli on specific populations of neurons in the rat striatum.
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Differential regulation of Preprotachykinin-A mRNA expression in striatum by excitation of hippocampal neurons.
European Journal of Neuroscience, 1993Co-Authors: Stefan Brené, Nils Lindefors, Mario Herrera-marschitz, Håkan PerssonAbstract:In this report we have studied the influence of hippocampal neurons on neuropeptide mRNA expression in both dorsal and ventral striatum in the rat. Intrahippocampal unilateral kainic acid injections were performed in control animals and in animals with a unilateral 6-hydroxydopamine-induced dopamine deafferentation of the striatum. In situ hybridization combined with quantitative image analysis was used to study the expression of Preprotachykinin A mRNA encoding the neuropeptides substance P and neurokinin A. The 6-hydroxydopamine-induced lesion caused a decrease of Preprotachykinin A mRNA levels in the ipsilateral dorsal striatum and in both sides of the ventral striatum. In normal rats, the intrahippocampal kainic acid injection caused a twofold increase in Preprotachykinin A mRNA in the limbic parts of the striatum, which are innervated by the hippocampus. No effect of the kainic acid injection was seen in the lateral parts of the dorsal striatum, a region which does not appear to be innvervated by the hippocampus. Animals with a 6-hydroxydopamine lesion showed a similar kainic acid-mediated increase in Preprotachykinin A mRNA in parts of the ventral striatum. In the dopamine-lesioned dorsal striatum and ventral striatum the decreased Preprotachykinin A mRNA levels were normalized by the intrahippocampal kainic acid injection. These results show that kainic acid-mediated excitation of hippocampal neurons causes a dopamine-independent induction of Preprotachykinin A mRNA expression in parts of the ventral striatum, and reverses the dopamine deafferentation-induced decrease of Preprotachykinin A mRNA in both dorsal and ventral striatum. Combined, our results suggest that hippocampal neurons can regulate Preprotachykinin A mRNA expression in both the ventral and the dorsal striatum.
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Amphetamine and haloperidol modulate Preprotachykinin A mRNA expression in rat nucleus accumbens and caudate-putamen.
Molecular Brain Research, 1992Co-Authors: Nils LindeforsAbstract:In situ hybridization was used to measure the effect of repeated amphetamine (1.5 mg/kg) and haloperidol (0.5 mg/kg) treatment for 7 days on the expression of Preprotachykinin A (PPT-A) mRNA in rat nucleus accumbens (Acb) and caudate-putamen (CPu). Amphetamine elevated the level of PPT-A mRNA in Acb, but not in CPu. Haloperidol decreased the levels in Acb shell and CPu, but not in Acb core. Haloperidol injected together with amphetamine, prevented the amphetamine-induced increase in PPT-A mRNA expression in both Acb core and shell.
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Kainic acid-mediated increase of Preprotachykinin-A messenger RNA expression in the rat hippocampus and a region-selective attenuation by dexamethasone.
Neuroscience, 1992Co-Authors: Stefan Brené, Nils Lindefors, M. Ballarin, Helena PerssonAbstract:Abstract The hippocampus contains the highest number of glucocorticoid-sensitive neurons in the rat brain and excessive exposure to glucocorticoids can cause damage to hippocampal neurons and impair the capacity of the hippocampus to survive neuronal insults. In this study in situ hybridization combined with quantitative image analysis was used to study Preprotachykinin-A mRNA levels after administration of a toxic dose of kainic acid in animals pretreated with glucocorticoids. Kainic acid was injected into dorsal hippocampus CA3 region in animals pretreated with the synthetic glucocorticoid receptor agonist dexamethasone and in control animals. Preprotachykinin-A mRNA was not detected in the hippocampus of untreated animals or in animals analysed 30 min after a kainic acid injection. However, 4 h after injection of kainic acid, the level of Preprotachykinin-A mRNA increased to 20-times above the detection limit both in the dentate gyrus and the CA3 region of the hippocampus. Treatment of kainic acid-injected animals with dexamethasone 30 min before and 2 h after the injection attenuated the increase in the granule cells of the dentate gyrus by 50%. In contrast, dexamethasone pretreatment had no significant effect on the kainic acid-induced increase of Preprotachykinin-A mRNA in pyramidal cells in regions CA3 or CA1. These results show that an excitatory stimulus within the hippocampus causes a substantial increase in the level of Preprotachykinin-A mRNA in hippocampal granule and pyramidal cells and suggest that in granule cells of the dentate gyrus this increase can be modulated by glucocorticoids.
Kristen A. Keefe - One of the best experts on this subject based on the ideXlab platform.
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Long‐term post‐synaptic consequences of methamphetamine on Preprotachykinin mRNA expression
Journal of Neurochemistry, 2002Co-Authors: Kamisha L. Johnson-davis, Glen R. Hanson, Kristen A. KeefeAbstract:Exposure to repeated high doses of methamphetamine produces long-term toxicity to central monoamine systems and alters striatonigral pathway function 3 weeks after exposure. To determine whether these changes in the striatonigral pathway persist for longer we examined neuropeptide mRNA expression in the striatum and cytochrome oxidase activity in the output nuclei of the basal ganglia after treatment with multiple high doses of methamphetamine. Rats exposed to multiple high doses of methamphetamine had significant depletion in dopamine and serotonin content, decreases in tyrosine hydroxylase immunoreactivity, and decreases in Preprotachykinin mRNA expression, 6 and 12 weeks after methamphetamine treatment. Preprotachykinin mRNA expression was significantly reduced by approximately 20% in the middle striatum and approximately 32% in the caudal striatum, 6 weeks after treatment. Twelve weeks after treatment, Preprotachykinin mRNA expression continued to be significantly reduced by approximately 20% in the middle striatum and approximately 14% in the caudal striatum. Cytochrome oxidase histochemical staining in the entopeduncular nucleus and substantia nigra pars reticulata was not significantly different from that in controls at either time point. These data suggest that neurotoxic regimens of methamphetamine induce changes in striatonigral neurons that persist for up to 3 months, although there is some recovery.
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long term post synaptic consequences of methamphetamine on Preprotachykinin mrna expression
Journal of Neurochemistry, 2002Co-Authors: Kamisha L Johnsondavis, Glen R. Hanson, Kristen A. KeefeAbstract:Exposure to repeated high doses of methamphetamine produces long-term toxicity to central monoamine systems and alters striatonigral pathway function 3 weeks after exposure. To determine whether these changes in the striatonigral pathway persist for longer we examined neuropeptide mRNA expression in the striatum and cytochrome oxidase activity in the output nuclei of the basal ganglia after treatment with multiple high doses of methamphetamine. Rats exposed to multiple high doses of methamphetamine had significant depletion in dopamine and serotonin content, decreases in tyrosine hydroxylase immunoreactivity, and decreases in Preprotachykinin mRNA expression, 6 and 12 weeks after methamphetamine treatment. Preprotachykinin mRNA expression was significantly reduced by approximately 20% in the middle striatum and approximately 32% in the caudal striatum, 6 weeks after treatment. Twelve weeks after treatment, Preprotachykinin mRNA expression continued to be significantly reduced by approximately 20% in the middle striatum and approximately 14% in the caudal striatum. Cytochrome oxidase histochemical staining in the entopeduncular nucleus and substantia nigra pars reticulata was not significantly different from that in controls at either time point. These data suggest that neurotoxic regimens of methamphetamine induce changes in striatonigral neurons that persist for up to 3 months, although there is some recovery.
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differential effects of cocaine and methamphetamine on neurotensin neuromedin n and Preprotachykinin messenger rna expression in unique regions of the striatum
Neuroscience, 2001Co-Authors: David H. Adams, Glen R. Hanson, Kristen A. KeefeAbstract:This study employed in situ hybridization to directly compare the effects of cocaine and methamphetamine on neurotensin/neuromedin N and Preprotachykinin messenger RNAs in distinct striatal regions. Male, Sprague-Dawley rats received a single administration of 15mg/kg methamphetamine (s.c.) or 30mg/kg cocaine (i.p.) and were killed 30min or 3h later. Methamphetamine and cocaine produced significant increases in Preprotachykinin messenger RNA in the striatum after 3h, but often in different subregions. Both drugs produced similar effects on Preprotachykinin messenger RNA in the rostral striatum. However, methamphetamine produced significant increases in all regions of the caudal striatum, whereas cocaine-induced Preprotachykinin messenger RNA expression was limited to dorsal regions of this striatal area. Methamphetamine also produced a significant increase in Preprotachykinin messenger RNA in the caudal striatum after 30min, whereas cocaine had no significant effect on Preprotachykinin messenger RNA at this early time-point. The pattern of changes in neurotensin/neuromedin N messenger RNA caused by methamphetamine and cocaine after 3h was even more distinct. Cocaine produced significant increases in neurotensin/neuromedin N messenger RNA in all regions of the rostral striatum, whereas methamphetamine had no effect in these areas. Furthermore, in more caudal sections, cocaine predominantly affected neurotensin/neuromedin N expression in dorsal aspects of the striatum, whereas methamphetamine significantly increased neurotensin/neuromedin N messenger RNA in all regions. There was much less effect of either drug on neuropeptide expression in the nucleus accumbens. The only significant effect was an increase in neurotensin/neuromedin N messenger RNA in the core region 3h after methamphetamine administration. These results indicate that methamphetamine and cocaine increase Preprotachykinin and neurotensin/neuromedin N messenger RNAs in distinct regions of the striatum. The ability of methamphetamine and cocaine to alter neuropeptide messenger RNA expression in unique regions of the striatum may be important for the long-term effects of these drugs, such as sensitization, since the striatum is not homogeneous in its connections and function.
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Differential effects of cocaine and methamphetamine on neurotensin/neuromedin N and Preprotachykinin messenger RNA expression in unique regions of the striatum.
Neuroscience, 2001Co-Authors: David H. Adams, Glen R. Hanson, Kristen A. KeefeAbstract:This study employed in situ hybridization to directly compare the effects of cocaine and methamphetamine on neurotensin/neuromedin N and Preprotachykinin messenger RNAs in distinct striatal regions. Male, Sprague-Dawley rats received a single administration of 15mg/kg methamphetamine (s.c.) or 30mg/kg cocaine (i.p.) and were killed 30min or 3h later. Methamphetamine and cocaine produced significant increases in Preprotachykinin messenger RNA in the striatum after 3h, but often in different subregions. Both drugs produced similar effects on Preprotachykinin messenger RNA in the rostral striatum. However, methamphetamine produced significant increases in all regions of the caudal striatum, whereas cocaine-induced Preprotachykinin messenger RNA expression was limited to dorsal regions of this striatal area. Methamphetamine also produced a significant increase in Preprotachykinin messenger RNA in the caudal striatum after 30min, whereas cocaine had no significant effect on Preprotachykinin messenger RNA at this early time-point. The pattern of changes in neurotensin/neuromedin N messenger RNA caused by methamphetamine and cocaine after 3h was even more distinct. Cocaine produced significant increases in neurotensin/neuromedin N messenger RNA in all regions of the rostral striatum, whereas methamphetamine had no effect in these areas. Furthermore, in more caudal sections, cocaine predominantly affected neurotensin/neuromedin N expression in dorsal aspects of the striatum, whereas methamphetamine significantly increased neurotensin/neuromedin N messenger RNA in all regions. There was much less effect of either drug on neuropeptide expression in the nucleus accumbens. The only significant effect was an increase in neurotensin/neuromedin N messenger RNA in the core region 3h after methamphetamine administration. These results indicate that methamphetamine and cocaine increase Preprotachykinin and neurotensin/neuromedin N messenger RNAs in distinct regions of the striatum. The ability of methamphetamine and cocaine to alter neuropeptide messenger RNA expression in unique regions of the striatum may be important for the long-term effects of these drugs, such as sensitization, since the striatum is not homogeneous in its connections and function.
Anne E. King - One of the best experts on this subject based on the ideXlab platform.
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neurotrophin induced Preprotachykinin a gene promoter modulation in organotypic rat spinal cord culture
Journal of Neurochemistry, 2006Co-Authors: Kathryn J. Hilton, Alan N. Bateson, Anne E. KingAbstract:To study regulation of the Preprotachykinin-A gene promoter, we utilised a biolistic gene transfer protocol to deliver a DNA construct that incorporates a portion of the Preprotachykinin-A gene promoter and an enhanced green fluorescent protein reporter gene into neonatal rat spinal cord organotypic slices. The ability of the neurokinin-1 receptor agonist [Sar9,Met(O2)11]-substance P, nerve growth factor and brain derived neurotrophic factor to modulate positively Preprotachykinin-A gene promoter construct activity, as indicated by de novo enhanced green fluorescent protein expression, was determined. Treatment of organotypic slices with [Sar9, Met(O2)11]-substance P (10 μm, P < 0.05), nerve growth factor (200 ng/mL, P < 0.001) or brain derived neurotrophic factor (200 ng/mL, P < 0.02) significantly increased the proportion of cytomegaloviral promoter-DsRed transfected cells (used to visualise total transfected cells) that co-expressed enhanced green fluorescent protein. The distribution of enhanced green fluorescent protein/DsRed-positive neurones across spinal laminae was broadly in line with the known distribution of spinal Trk and neurokinin-1 receptors. These data suggest a modulated activity of the Preprotachykinin-A gene promoter in spinal neurones in vitro by substance P and/or neurotrophins. The functional consequences of such transcriptional changes within central peptidergic circuitry and their relevance to chronic pain are considered.
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Neurotrophin-induced Preprotachykinin-A gene promoter modulation in organotypic rat spinal cord culture.
Journal of Neurochemistry, 2006Co-Authors: Kathryn J. Hilton, Alan N. Bateson, Anne E. KingAbstract:To study regulation of the Preprotachykinin-A gene promoter, we utilised a biolistic gene transfer protocol to deliver a DNA construct that incorporates a portion of the Preprotachykinin-A gene promoter and an enhanced green fluorescent protein reporter gene into neonatal rat spinal cord organotypic slices. The ability of the neurokinin-1 receptor agonist [Sar9,Met(O2)11]-substance P, nerve growth factor and brain derived neurotrophic factor to modulate positively Preprotachykinin-A gene promoter construct activity, as indicated by de novo enhanced green fluorescent protein expression, was determined. Treatment of organotypic slices with [Sar9, Met(O2)11]-substance P (10 μm, P
Bertil B. Fredholm - One of the best experts on this subject based on the ideXlab platform.
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involvement of a c fos dependent mechanism in caffeine induced expression of the Preprotachykinin a and neurotensin neuromedin n genes in rat striatum
European Journal of Neuroscience, 1997Co-Authors: Per Svenningsson, Jeanette Georgieva, Ewa Kontnyi, Markus Heilig, Bertil B. FredholmAbstract:Striatal c-fos induction was blocked by local administration of phosphorothioated c-fos antisense oligonucleotides (AS-ODN) to examine the possible role of caffeine-induced c-fos expression in transcriptional regulation of striatal preproenkephalin, prodynorphin, Preprotachykinin A and neurotensin/neuromedin N. Caffeine (100 mg/kg i.p.) induced both c-fos mRNA and Fos-protein, and this induction was significantly attenuated by intrastriatal injection of 4 (but not 1) nmol c-fos AS-ODN. This suggests that, in addition to translational arrest, other mechanisms may be involved in the mediation of antisense action. The action of the AS-ODN was sequence specific. The antisense blockade of c-fos reduced the effect of caffeine on the expression of mRNAs for Preprotachykinin A and neurotensin/neuromedin N in the ventrolateral caudate-putamen. Levels of preproenkephalin and prodynorphin transcripts were unaffected. Thus caffeine induction of striatal Preprotachykinin A mRNA and neurotensin/neuromedin N mRNA, but not of preproenkephalin mRNA or prodynorphin mRNA, may at least in part be mediated by a pathway involving Fos protein. The findings illustrate the utility of blockade of gene expression with antisense oligonucleotides for in vivo studies of drug actions.
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Involvement of a c-fos-dependent mechanism in caffeine-induced expression of the Preprotachykinin A and neurotensin/neuromedin N genes in rat striatum.
European Journal of Neuroscience, 1997Co-Authors: Per Svenningsson, Jeanette Georgieva, Ewa Kontnyi, Markus Heilig, Bertil B. FredholmAbstract:Striatal c-fos induction was blocked by local administration of phosphorothioated c-fos antisense oligonucleotides (AS-ODN) to examine the possible role of caffeine-induced c-fos expression in transcriptional regulation of striatal preproenkephalin, prodynorphin, Preprotachykinin A and neurotensin/neuromedin N. Caffeine (100 mg/kg i.p.) induced both c-fos mRNA and Fos-protein, and this induction was significantly attenuated by intrastriatal injection of 4 (but not 1) nmol c-fos AS-ODN. This suggests that, in addition to translational arrest, other mechanisms may be involved in the mediation of antisense action. The action of the AS-ODN was sequence specific. The antisense blockade of c-fos reduced the effect of caffeine on the expression of mRNAs for Preprotachykinin A and neurotensin/neuromedin N in the ventrolateral caudate-putamen. Levels of preproenkephalin and prodynorphin transcripts were unaffected. Thus caffeine induction of striatal Preprotachykinin A mRNA and neurotensin/neuromedin N mRNA, but not of preproenkephalin mRNA or prodynorphin mRNA, may at least in part be mediated by a pathway involving Fos protein. The findings illustrate the utility of blockade of gene expression with antisense oligonucleotides for in vivo studies of drug actions.