The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Roland Brandt - One of the best experts on this subject based on the ideXlab platform.
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rna protein granules modulate tau isoform expression and induce Neuronal Sprouting
Journal of Biological Chemistry, 2014Co-Authors: Katharina Moschner, Frederik Sundermann, Heiko Meyer, Abel Pereira Da Graca, Neele Appel, Achim Paululat, Lidia Bakota, Roland BrandtAbstract:Abstract The Neuronal microtubule-associated protein tau is expressed in different variants and changes in tau isoform composition occur during development and disease. Here, we investigate a potential role of the multivalent tau mRNA-binding proteins G3BP1 and IMP1 in regulating Neuronal tau expression. We demonstrate that G3BP1 and IMP1 expression induces the formation of structures, which qualify as Neuronal RNA-protein (RNP) granules and concentrate multivalent proteins and mRNA. We show that RNP granule formation leads to a >30-fold increase in the ratio of high molecular weight (HMW) to low molecular weight (LMW) tau mRNA and a ~12-fold increase in HMW to LMW tau protein. We report that RNP granule formation is associated with increased neurite formation and enhanced process growth. G3BP1 deletion constructs that do not induce granule formation are also deficient to induce Neuronal Sprouting or to change the expression pattern of tau. The data indicate that granule formation driven by multivalent proteins modulates tau isoform expression and suggest a morphoregulatory function of RNP granules during health and disease.
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RNA Protein Granules Modulate tau Isoform Expression and Induce Neuronal Sprouting
The Journal of biological chemistry, 2014Co-Authors: Katharina Moschner, Frederik Sundermann, Heiko Meyer, Abel Pereira Da Graca, Neele Appel, Achim Paululat, Lidia Bakota, Roland BrandtAbstract:The Neuronal microtubule-associated protein Tau is expressed in different variants, and changes in Tau isoform composition occur during development and disease. Here, we investigate a potential role of the multivalent tau mRNA-binding proteins G3BP1 and IMP1 in regulating Neuronal tau expression. We demonstrate that G3BP1 and IMP1 expression induces the formation of structures, which qualify as Neuronal ribonucleoprotein (RNP) granules and concentrate multivalent proteins and mRNA. We show that RNP granule formation leads to a >30-fold increase in the ratio of high molecular weight to low molecular weight tau mRNA and an ∼12-fold increase in high molecular weight to low molecular weight Tau protein. We report that RNP granule formation is associated with increased neurite formation and enhanced process growth. G3BP1 deletion constructs that do not induce granule formation are also deficient in inducing Neuronal Sprouting or changing the expression pattern of tau. The data indicate that granule formation driven by multivalent proteins modulates tau isoform expression and suggest a morphoregulatory function of RNP granules during health and disease.
Michael W. Baker - One of the best experts on this subject based on the ideXlab platform.
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Expression levels of a LAR-like receptor protein tyrosine phosphatase correlate with Neuronal branching and arbor density in the medicinal leech.
Developmental biology, 2010Co-Authors: Michael W. Baker, Eduardo R. MacagnoAbstract:LAR-like receptor protein tyrosine phosphatases (RPTPs), which are reported to be highly expressed in the nervous systems of most bilaterian animals, have been implicated in the regulation of critical developmental processes, such as Neuronal pathfinding, cell adhesion and synaptogenesis. Here we report that two LAR-like RPTPs in the medicinal leech, HmLAR1 and HmLAR2, play roles in regulating the size and density of Neuronal arbors within the developing nervous system and in the body wall. Employing single-cell RNAi knockdown and transgene expression techniques, we demonstrate that the expression level of HmLAR1 is directly correlated with the density of an identified neuron's arborization. Knocking down HmLAR1 mRNA levels in the mechanosensory pressure (P) neurons produces a reduced central arbor and a smaller arbor in the peripheral body wall, with fewer terminal branches. By contrast, overexpression of this receptor in a P cell leads to extensive Neuronal Sprouting, including many supernumerary neurites and terminal branches as well as, in some instances, the normal monopolar morphology of the P cell becoming multipolar. We also report that induced Neuronal Sprouting requires the expression of the receptor's membrane tethered ectodomain, including the NH(2)-Ig domains, but not of the intracellular phosphatase domains of the receptor. Interestingly, Sprouting could be elicited upon ectopic expression of HmLAR1 and the related RPTP, HmLAR2 in the P and other neurons, including those that do not normally express either RPTP, suggesting that the substrates involved in HmLAR-induced Sprouting are present in most neurons irrespective of whether they normally express these LAR-like RPTPs. Our data are consistent with the hypothesis that the receptors' ectodomains promote an adhesive interaction that enhances the maintenance of new processes.
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Modulation ofin vivo Neuronal Sprouting by serotonin in the adult CNS of the snail
Cellular and Molecular Neurobiology, 1996Co-Authors: Michael W. Baker, Roger P. CrollAbstract:1. During in situ recovery from a lesion to the cerebrobuccal connective (CBC) in the snail Achatina fulica , neurons of the buccal ganglia undergo extensive regeneration and Sprouting as assessed by axonal dye-fillings of the CBC. 2. These changes are preceded by the distal degeneration of severed fibres from the serotonergic metacerebral giant neuron (MCG), which results in the depletion of serotonin (5-HT) in the ipsilateral buccal ganglion. We have investigated the potential role of this depletion in causing some of the ensuing neuroplastic events. 3. Pharmacological depletion of 5-HT using either 5,7-dihydroxtryptamine or p-chlorophenylalanine in normal, unlesioned animals was found to produce supernumerary Neuronal labelling similar to that seen following a lesion. 4. Systemic daily injections of 5-HT were found to partly suppress the Sprouting response following the CBC lesion. For example, the contralateral uninjured MCG which is normally induced by the lesion to sprout novel projections into the denervated ganglion, is suppressed from doing so by the 5-HT treatment. 5. These growth inhibiting effects of 5-HT upon the contralateral MCG could be antagonized by the prior administration of the 5-HT receptor blocker cyproheptadine, suggesting a specific receptor mediated action. 6. We suggest that 5-HT may play a role in governing the state of Neuronal outgrowth in vivo in the CNS of the adult snail, as has been suggested by early developmental and Neuronal cultural studies.
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Modulation of in vivo Neuronal Sprouting by serotonin in the adult CNS of the snail.
Cellular and molecular neurobiology, 1996Co-Authors: Michael W. Baker, Roger P. CrollAbstract:1. During in situ recovery from a lesion to the cerebrobuccal connective (CBC) in the snail Achatina fulica, neurons of the buccal ganglia undergo extensive regeneration and Sprouting as assessed by axonal dye-fillings of the CBC. 2. These changes are preceded by the distal degeneration of severed fibres from the serotonergic metacerebral giant neuron (MCG), which results in the depletion of serotonin (5-HT) in the ipsilateral buccal ganglion. We have investigated the potential role of this depletion in causing some of the ensuing neuroplastic events. 3. Pharmacological depletion of 5-HT using either 5,7-dihydroxtryptamine or p-chlorophenylalanine in normal, unlesioned animals was found to produce supernumerary Neuronal labelling similar to that seen following a lesion. 4. Systemic daily injections of 5-HT were found to partly suppress the Sprouting response following the CBC lesion. For example, the contralateral, uninjured MCG which is normally induced by the lesion to sprout novel projections into the denervated ganglion, is suppressed from doing so by the 5-HT treatment. 5. These growth inhibiting effects of 5-HT upon the contralateral MCG could be antagonized by the prior administration of the 5-HT receptor blocker cyproheptadine, suggesting a specific receptor mediated action. 6. We suggest that 5-HT may play a role in governing the state of Neuronal outgrowth in vivo in the CNS of the adult snail, as has been suggested by early development and Neuronal cultural studies.
Greg M. Cole - One of the best experts on this subject based on the ideXlab platform.
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Defective Neuronal Sprouting by human apolipoprotein E4 is a gain-of-negative function
Journal of neuroscience research, 2002Co-Authors: Bruce Teter, John Gilbert, A. D. Roses, Douglas Galasko, Greg M. ColeAbstract:The apolipoprotein E (apoE) epsilon 4 allele (apoE4) is a major risk factor for neurodegenerative conditions, including Alzheimer's disease (AD). A role for apoE in regeneration of synaptic circuitry after neural injury has been shown in several in vitro studies in which apoE3 supports Neuronal Sprouting better than apoE4. We evaluated Sprouting in an in vitro mouse organotypic hippocampal slice culture system derived from transgenic mice expressing apoE3 or apoE4, in which apoE-dependent granule cell mossy fiber Sprouting in the presence of apoE4 is only 51% of the level of apoE3. Sprouting supported by apoE4 had a dose response opposite that by supported by apoE3: although increasing E3 expression increased Sprouting, increasing E4 expression decreased Sprouting, suggesting that the defect in E4 in supporting Neuronal Sprouting is a gain-of-negative activity. These results may have important pharmacogenomic implications for AD therapies that modulate apoE expression levels.
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human apolipoprotein e isoform specific differences in Neuronal Sprouting in organotypic hippocampal culture
Journal of Neurochemistry, 2002Co-Authors: Bruce Teter, John Gilbert, A. D. Roses, Douglas Galasko, Puting Xu, Greg M. ColeAbstract:Abstract : The apolipoprotein E (ApoE) e4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer's disease. A role for ApoE is implicated in regeneration of synaptic circuitry after neural injury. In the in vitro mouse organotypic hippocampal slice culture system, we previously showed that cultures derived from ApoE-knockout mice are defective in mossy fiber Sprouting into the dentate gyrus molecular layer. This Sprouting defect was rescued in cultures from transgenic mice expressing ApoE3 under the control of the human promoter and in ApoE-knockout cultures treated with ApoE3-conditioned media. Although the ApoE3 transgene fully restored Sprouting, ApoE4 restored Sprouting to only 58% of ApoE3 levels. These data indicate that ApoE isoform-specific effects on neuroregeneration may contribute to its genetic risk for Alzheimer's disease.
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Human Apolipoprotein E Isoform‐Specific Differences in Neuronal Sprouting in Organotypic Hippocampal Culture
Journal of neurochemistry, 2002Co-Authors: Bruce Teter, John Gilbert, A. D. Roses, Douglas Galasko, Greg M. ColeAbstract:Abstract : The apolipoprotein E (ApoE) e4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer's disease. A role for ApoE is implicated in regeneration of synaptic circuitry after neural injury. In the in vitro mouse organotypic hippocampal slice culture system, we previously showed that cultures derived from ApoE-knockout mice are defective in mossy fiber Sprouting into the dentate gyrus molecular layer. This Sprouting defect was rescued in cultures from transgenic mice expressing ApoE3 under the control of the human promoter and in ApoE-knockout cultures treated with ApoE3-conditioned media. Although the ApoE3 transgene fully restored Sprouting, ApoE4 restored Sprouting to only 58% of ApoE3 levels. These data indicate that ApoE isoform-specific effects on neuroregeneration may contribute to its genetic risk for Alzheimer's disease.
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Role of apolipoprotein E and estrogen in mossy fiber Sprouting in hippocampal slice cultures.
Neuroscience, 1999Co-Authors: Bruce Teter, Marni E. Harris-white, Sally A. Frautschy, Greg M. ColeAbstract:Abstract A role for apolipoprotein E is implicated in regeneration of synaptic circuitry after neural injury. The in vitro mouse organotypic hippocampal slice culture system shows Timm's stained mossy fiber Sprouting into the dentate gyrus molecular layer in response to deafferentation of the entorhinal cortex. We show that cultures derived from apolipoprotein E knockout mice are defective in this Sprouting response; specifically, they show no Sprouting in the dorsal region of the dentate gyrus, yet retain Sprouting in the ventral region. Dorsal but not ventral Sprouting in cultures from C57Bl/6J mice is increased 75% by treatment with 100 pM 17β-estradiol; this response is blocked by both progesterone and tamoxifen. These results show that Neuronal Sprouting is increased by estrogen in the same region where Sprouting is dependent on apolipoprotein E. Sprouting may be stimulated by estrogen through its up-regulation of apolipoprotein E expression leading to increased recycling of membrane lipids for use by Sprouting neurons. Estrogen and apolipoprotein E may therefore interact in their modulation of both Alzheimer's disease risk and recovery from CNS injury.
Roger P. Croll - One of the best experts on this subject based on the ideXlab platform.
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Modulation ofin vivo Neuronal Sprouting by serotonin in the adult CNS of the snail
Cellular and Molecular Neurobiology, 1996Co-Authors: Michael W. Baker, Roger P. CrollAbstract:1. During in situ recovery from a lesion to the cerebrobuccal connective (CBC) in the snail Achatina fulica , neurons of the buccal ganglia undergo extensive regeneration and Sprouting as assessed by axonal dye-fillings of the CBC. 2. These changes are preceded by the distal degeneration of severed fibres from the serotonergic metacerebral giant neuron (MCG), which results in the depletion of serotonin (5-HT) in the ipsilateral buccal ganglion. We have investigated the potential role of this depletion in causing some of the ensuing neuroplastic events. 3. Pharmacological depletion of 5-HT using either 5,7-dihydroxtryptamine or p-chlorophenylalanine in normal, unlesioned animals was found to produce supernumerary Neuronal labelling similar to that seen following a lesion. 4. Systemic daily injections of 5-HT were found to partly suppress the Sprouting response following the CBC lesion. For example, the contralateral uninjured MCG which is normally induced by the lesion to sprout novel projections into the denervated ganglion, is suppressed from doing so by the 5-HT treatment. 5. These growth inhibiting effects of 5-HT upon the contralateral MCG could be antagonized by the prior administration of the 5-HT receptor blocker cyproheptadine, suggesting a specific receptor mediated action. 6. We suggest that 5-HT may play a role in governing the state of Neuronal outgrowth in vivo in the CNS of the adult snail, as has been suggested by early developmental and Neuronal cultural studies.
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Modulation of in vivo Neuronal Sprouting by serotonin in the adult CNS of the snail.
Cellular and molecular neurobiology, 1996Co-Authors: Michael W. Baker, Roger P. CrollAbstract:1. During in situ recovery from a lesion to the cerebrobuccal connective (CBC) in the snail Achatina fulica, neurons of the buccal ganglia undergo extensive regeneration and Sprouting as assessed by axonal dye-fillings of the CBC. 2. These changes are preceded by the distal degeneration of severed fibres from the serotonergic metacerebral giant neuron (MCG), which results in the depletion of serotonin (5-HT) in the ipsilateral buccal ganglion. We have investigated the potential role of this depletion in causing some of the ensuing neuroplastic events. 3. Pharmacological depletion of 5-HT using either 5,7-dihydroxtryptamine or p-chlorophenylalanine in normal, unlesioned animals was found to produce supernumerary Neuronal labelling similar to that seen following a lesion. 4. Systemic daily injections of 5-HT were found to partly suppress the Sprouting response following the CBC lesion. For example, the contralateral, uninjured MCG which is normally induced by the lesion to sprout novel projections into the denervated ganglion, is suppressed from doing so by the 5-HT treatment. 5. These growth inhibiting effects of 5-HT upon the contralateral MCG could be antagonized by the prior administration of the 5-HT receptor blocker cyproheptadine, suggesting a specific receptor mediated action. 6. We suggest that 5-HT may play a role in governing the state of Neuronal outgrowth in vivo in the CNS of the adult snail, as has been suggested by early development and Neuronal cultural studies.
Margaret A. Vizzard - One of the best experts on this subject based on the ideXlab platform.
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Intravesical PAC1 Receptor Antagonist, PACAP(6–38), Reduces Urinary Bladder Frequency and Pelvic Sensitivity in NGF-OE Mice
Journal of Molecular Neuroscience, 2016Co-Authors: Beatrice M. Girard, Susan E. Malley, Morgan M. Mathews, Margaret A. VizzardAbstract:Chronic NGF overexpression (OE) in the urothelium, achieved through the use of a highly urothelium-specific uroplakin II promoter, stimulates Neuronal Sprouting in the urinary bladder, produces increased voiding frequency and non-voiding contractions, and referred somatic sensitivity. Additional NGF-mediated pleiotropic changes might contribute to increased voiding frequency and pelvic hypersensitivity in NGF-OE mice such as neuropeptide/receptor systems including PACAP(Adcyap1) and PAC1 receptor (Adcyap1r1). Given the presence of PAC1-immunoreactive fibers and the expression of PAC1 receptor expression in bladder tissues, and PACAP-facilitated detrusor contraction, whether PACAP/receptor signaling contributes to increased voiding frequency and somatic sensitivity was evaluated in NGF-OE mice. Intravesical administration of the PAC1 receptor antagonist, PACAP(6–38) (300 nM), significantly ( p ≤ 0.01) increased intercontraction interval (2.0-fold) and void volume (2.5-fold) in NGF-OE mice. Intravesical instillation of PACAP(6–38) also decreased baseline bladder pressure in NGF-OE mice. PACAP(6–38) had no effects on bladder function in WT mice. Intravesical administration of PACAP(6–38) (300 nM) significantly ( p ≤ 0.01) reduced pelvic sensitivity in NGF-OE mice but was without effect in WT mice. PACAP/receptor signaling contributes to the increased voiding frequency and pelvic sensitivity observed in NGF-OE mice.
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Neurotrophin/receptor expression in urinary bladder of mice with overexpression of NGF in urothelium.
American journal of physiology. Renal physiology, 2010Co-Authors: Beatrice M. Girard, Susan E. Malley, Margaret A. VizzardAbstract:Urothelium-specific overexpression of nerve growth factor (NGF) in the urinary bladder of transgenic mice stimulates Neuronal Sprouting in the urinary bladder, produces increased voiding frequency,...