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Robertbenjamin Illing - One of the best experts on this subject based on the ideXlab platform.
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superior olivary contributions to auditory system plasticity medial but not lateral olivocochlear neurons are the source of cochleotomy induced gap 43 expression in the ventral cochlear nucleus
The Journal of Comparative Neurology, 2004Co-Authors: Kari Suzanne Kraus, Robertbenjamin IllingAbstract:A unilateral cochlear lesion induces expression of the growth and plasticity-associated Protein 43 (Gap-43) in fibers and their varicosities on specific types of postsynaptic profiles in the ventral cochlear nucleus (VCN), suggesting the induction of synaptic remodeling. One candidate population from which Gap-43 might emerge was neurons of the lateral olivocochlear (LOC) system residing in the lateral superior olive (LSO). Upon cochleotomy, these neurons express Gap-43 mRNA and Gap-43 Protein. However, retrograde axonal tracing with Fast Blue or biotinylated dextran amine from VCN revealed that the number of 6.8 +/- 1.3 neurons in the whole ipsilateral LSO labeled in normal adult rats was distinctly small and did not rise after cochleotomy. Concluding that LOC neurons cannot be the source of Gap-43 in the VCN, we reinvestigated the pattern of Gap-43 in situ hybridization and found that, after cochleotomy, shell neurons in the regions surrounding the LSO and medial olivocochlear (MOC) neurons in the ventral nucleus of the trapezoid body up-regulated Gap-43 mRNA. We then lesioned these regions by means of stereotaxic injections of kainic acid. Destruction of shell neurons preceding an ipsilateral cochleotomy did not change the emergence of Gap-43 immunoreactivity in the VCN. However, if the contralateral MOC system was lesioned, the rise of Gap-43 immunoreactivity in VCN on the side of the cochleotomy was significantly reduced. We conclude that, after cochlear dysfunction, MOC neurons are the major (if not exclusive) source of synaptic reorganization in the VCN that could possibly entail compensatory activation of the affected ascending auditory pathway.
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superior olivary contributions to auditory system plasticity medial but not lateral olivocochlear neurons are the source of cochleotomy induced gap 43 expression in the ventral cochlear nucleus
The Journal of Comparative Neurology, 2004Co-Authors: Kari Suzanne Kraus, Robertbenjamin IllingAbstract:A unilateral cochlear lesion induces expression of the growth and plasticity-associated Protein 43 (Gap-43) in fibers and their varicosities on specific types of postsynaptic profiles in the ventral cochlear nucleus (VCN), suggesting the induction of synaptic remodeling. One candidate population from which Gap-43 might emerge was neurons of the lateral olivocochlear (LOC) system residing in the lateral superior olive (LSO). Upon cochleotomy, these neurons express Gap-43 mRNA and Gap-43 Protein. However, retrograde axonal tracing with Fast Blue or biotinylated dextran amine from VCN revealed that the number of 6.8 ± 1.3 neurons in the whole ipsilateral LSO labeled in normal adult rats was distinctly small and did not rise after cochleotomy. Concluding that LOC neurons cannot be the source of Gap-43 in the VCN, we reinvestigated the pattern of Gap-43 in situ hybridization and found that, after cochleotomy, shell neurons in the regions surrounding the LSO and medial olivocochlear (MOC) neurons in the ventral nucleus of the trapezoid body up-regulated Gap-43 mRNA. We then lesioned these regions by means of stereotaxic injections of kainic acid. Destruction of shell neurons preceding an ipsilateral cochleotomy did not change the emergence of Gap-43 immunoreactivity in the VCN. However, if the contralateral MOC system was lesioned, the rise of Gap-43 immunoreactivity in VCN on the side of the cochleotomy was significantly reduced. We conclude that, after cochlear dysfunction, MOC neurons are the major (if not exclusive) source of synaptic reorganization in the VCN that could possibly entail compensatory activation of the affected ascending auditory pathway. J. Comp. Neurol. 475:374–390, 2004. © 2004 Wiley-Liss, Inc.
Kari Suzanne Kraus - One of the best experts on this subject based on the ideXlab platform.
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superior olivary contributions to auditory system plasticity medial but not lateral olivocochlear neurons are the source of cochleotomy induced gap 43 expression in the ventral cochlear nucleus
The Journal of Comparative Neurology, 2004Co-Authors: Kari Suzanne Kraus, Robertbenjamin IllingAbstract:A unilateral cochlear lesion induces expression of the growth and plasticity-associated Protein 43 (Gap-43) in fibers and their varicosities on specific types of postsynaptic profiles in the ventral cochlear nucleus (VCN), suggesting the induction of synaptic remodeling. One candidate population from which Gap-43 might emerge was neurons of the lateral olivocochlear (LOC) system residing in the lateral superior olive (LSO). Upon cochleotomy, these neurons express Gap-43 mRNA and Gap-43 Protein. However, retrograde axonal tracing with Fast Blue or biotinylated dextran amine from VCN revealed that the number of 6.8 +/- 1.3 neurons in the whole ipsilateral LSO labeled in normal adult rats was distinctly small and did not rise after cochleotomy. Concluding that LOC neurons cannot be the source of Gap-43 in the VCN, we reinvestigated the pattern of Gap-43 in situ hybridization and found that, after cochleotomy, shell neurons in the regions surrounding the LSO and medial olivocochlear (MOC) neurons in the ventral nucleus of the trapezoid body up-regulated Gap-43 mRNA. We then lesioned these regions by means of stereotaxic injections of kainic acid. Destruction of shell neurons preceding an ipsilateral cochleotomy did not change the emergence of Gap-43 immunoreactivity in the VCN. However, if the contralateral MOC system was lesioned, the rise of Gap-43 immunoreactivity in VCN on the side of the cochleotomy was significantly reduced. We conclude that, after cochlear dysfunction, MOC neurons are the major (if not exclusive) source of synaptic reorganization in the VCN that could possibly entail compensatory activation of the affected ascending auditory pathway.
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superior olivary contributions to auditory system plasticity medial but not lateral olivocochlear neurons are the source of cochleotomy induced gap 43 expression in the ventral cochlear nucleus
The Journal of Comparative Neurology, 2004Co-Authors: Kari Suzanne Kraus, Robertbenjamin IllingAbstract:A unilateral cochlear lesion induces expression of the growth and plasticity-associated Protein 43 (Gap-43) in fibers and their varicosities on specific types of postsynaptic profiles in the ventral cochlear nucleus (VCN), suggesting the induction of synaptic remodeling. One candidate population from which Gap-43 might emerge was neurons of the lateral olivocochlear (LOC) system residing in the lateral superior olive (LSO). Upon cochleotomy, these neurons express Gap-43 mRNA and Gap-43 Protein. However, retrograde axonal tracing with Fast Blue or biotinylated dextran amine from VCN revealed that the number of 6.8 ± 1.3 neurons in the whole ipsilateral LSO labeled in normal adult rats was distinctly small and did not rise after cochleotomy. Concluding that LOC neurons cannot be the source of Gap-43 in the VCN, we reinvestigated the pattern of Gap-43 in situ hybridization and found that, after cochleotomy, shell neurons in the regions surrounding the LSO and medial olivocochlear (MOC) neurons in the ventral nucleus of the trapezoid body up-regulated Gap-43 mRNA. We then lesioned these regions by means of stereotaxic injections of kainic acid. Destruction of shell neurons preceding an ipsilateral cochleotomy did not change the emergence of Gap-43 immunoreactivity in the VCN. However, if the contralateral MOC system was lesioned, the rise of Gap-43 immunoreactivity in VCN on the side of the cochleotomy was significantly reduced. We conclude that, after cochlear dysfunction, MOC neurons are the major (if not exclusive) source of synaptic reorganization in the VCN that could possibly entail compensatory activation of the affected ascending auditory pathway. J. Comp. Neurol. 475:374–390, 2004. © 2004 Wiley-Liss, Inc.
A R Lieberman - One of the best experts on this subject based on the ideXlab platform.
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Overexpression of Gap-43 in thalamic projection neurons of transgenic mice does not enable them to regenerate axons through peripheral nerve grafts
Experimental Neurology, 2000Co-Authors: M.r.j. Mason, G Campbell, P. Caroni, Patrick N. Anderson, A R LiebermanAbstract:It is well established that some populations of neurons of the adult rat central nervous system (CNS) will regenerate axons into a peripheral nerve implant, but others, including most thalamocortical projection neurons, will not. The ability to regenerate axons may depend on whether neurons can express growth-related genes such as Gap-43, whose expression correlates with axon growth during development and with competence to regenerate. Thalamic projection neurons which fail to regenerate into a graft also fail to upregulate Gap-43. We have tested the hypothesis that the absence of strong Gap-43 expression by the thalamic projection neurons prevents them from regenerating their axons, using transgenic mice which overexpress Gap-43. Transgene expression was mapped by in situ hybridization with a digoxigenin-labeled RNA probe and by immunohistochemistry with a monoclonal antibody against the Gap-43 Protein produced by the transgene. Many CNS neurons were found to express the mRNA and Protein, including neurons of the mediodorsal and ventromedial thalamic nuclei, which rarely regenerate axons into peripheral nerve grafts. Grafts were implanted into the region of these nuclei in the brains of transgenic animals. Although these neurons strongly expressed the transgene mRNA and Protein and transported the Protein to their axon terminals, they did not regenerate axons into the graft, suggesting that lack of Gap-43 expression is not the only factor preventing thalamocortical neurons regenerating their axons.
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the effects of a lesion or a peripheral nerve graft on gap 43 upregulation in the adult rat brain an in situ hybridization and immunocytochemical study
The Journal of Neuroscience, 1995Co-Authors: E Vaudano, G Campbell, P N Anderson, Anthony Davies, C Woolhead, D J Schreyer, A R LiebermanAbstract:We have sought to determine (1) if thalamic neurons upregulate the growth associated Protein Gap-43 as a response to injury, or if a peripheral nerve graft is required to induce, enhance or sustain such a response, and (2) if thalamic neurons with different regenerative potentials also display different Gap-43 responses. Levels of Gap-43 Protein (detected by LM and EM immunohistochemistry) and of Gap-43 mRNA (detected by in situ hybridization) were compared in the thalamus of adult rats between 1 d and 180 d after making a stab lesion or after implanting a peripheral nerve autograft. Stab injury is a sufficient stimulus to cause a transient upregulation in Gap-43 expression by neurons in the thalamus (both around the graft tip and in particular in the thalamic reticular nucleus) in the first week after injury but this response is both prolonged, and enhanced in the presence of a peripheral nerve graft. In addition, we demonstrate directly, by double labelling, that neurons of the thalamic reticular nucleus displaying high levels of the mRNA for Gap-43, have axons regenerating in the distal portion of the graft. These findings lend direct support to the hypothesis that upregulation of the Gap-43 gene is essential for prolonged regenerative axonal growth. We also demonstrate Gap-43 Protein in graft Schwann cells and in brain astrocytes close to the site of graft implantation.
Nora I Perronebizzozero - One of the best experts on this subject based on the ideXlab platform.
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growth associated Protein 43 gap 43 and synaptophysin alterations in the dentate gyrus of patients with schizophrenia
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2005Co-Authors: Jessie S Chambers, Rachael L. Neve, Deirdre Thomas, L C Saland, Nora I PerronebizzozeroAbstract:Growth-associated Protein 43 (Gap-43) expression is critical for the proper establishment of neural circuitry, a process thought to be disrupted in schizophrenia. Previous work from our laboratory demonstrated decreased Gap-43 levels in post-mortem tissue from the entire hippocampal formation of affected individuals. In the present study, we used immunocytochemical techniques to localize alterations in Gap-43 Protein to specific synapses. Gap-43 distribution was compared to that of synaptophysin, another synaptic Protein known to be altered in schizophrenia. The levels and distribution of Gap-43 and synaptophysin Proteins were measured in the dentate gyrus of subjects with schizophrenia and sex-, age-, and postmortem interval-matched normal controls and subjects with bipolar disorder. Tissue from subjects was provided by the Harvard Brain Tissue Resource Center. In control subjects, Gap-43 immunostaining was prominent in synaptic terminals in the inner molecular layer and hilar region. Subjects with schizophrenia had significant decreases in Gap-43 immunoreactivity in the hilus (p<0.05, paired t-test) and inner molecular layer (p<0.05, paired t-test) but not in the outer molecular layer. In the same tissues, synaptophysin immunoreactivity was significantly reduced in both the inner and outer molecular layers of the dentate gyrus (both p<0.01 by paired t-test), but not in the hilus. In contrast to patients with schizophrenia, Gap-43 and synaptophysin levels in subjects with bipolar disorder did not differ from controls. Given the relationship of Gap-43 and synaptophysin with the development and plasticity of synaptic connections, the observed alterations in the hippocampus of patients with schizophrenia may be related to cognitive deficits associated with this illness.
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the rna binding Protein hud is required for gap 43 mrna stability gap 43 gene expression and pkc dependent neurite outgrowth in pc12 cells
Molecular Biology of the Cell, 2000Co-Authors: Charlotte D. Mobarak, Kim D. Anderson, M. Morin, Henry Furneaux, Andrea Beckelmitchener, Sherry L Rogers, Peter H King, Nora I PerronebizzozeroAbstract:The RNA-binding Protein HuD binds to a regulatory element in the 39 untranslated region (39 UTR) of the Gap-43 mRNA. To investigate the functional significance of this interaction, we generated PC12 cell lines in which HuD levels were controlled by transfection with either antisense (pDuH) or sense (pcHuD) constructs. pDuH-transfected cells contained reduced amounts of Gap-43 Protein and mRNA, and these levels remained low even after nerve growth factor (NGF) stimulation, a treatment that is normally associated with Protein kinase C (PKC)dependent stabilization of the Gap-43 mRNA and neuronal differentiation. Analysis of Gap-43 mRNA stability demonstrated that the mRNA had a shorter half-life in these cells. In agreement with their deficient Gap-43 expression, pDuH cells failed to grow neurites in the presence of NGF or phorbol esters. These cells, however, exhibited normal neurite outgrowth when exposed to dibutyryl-cAMP, an agent that induces outgrowth independently from Gap-43. We observed opposite effects in pcHuD-transfected cells. The Gap-43 mRNA was stabilized in these cells, leading to an increase in the levels of the Gap-43 mRNA and Protein. pcHuD cells were also found to grow short spontaneous neurites, a process that required the presence of Gap-43. In conclusion, our results suggest that HuD plays a critical role in PKC-mediated neurite outgrowth in PC12 cells and that this Protein does so primarily by promoting the stabilization of the Gap-43 mRNA.
Charlotte D. Mobarak - One of the best experts on this subject based on the ideXlab platform.
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Overexpression of HuD, but not of its truncated form HuD I+II, promotes Gap-43 gene expression and neurite outgrowth in PC12 cells in the absence of nerve growth factor.
Journal of neurochemistry, 2002Co-Authors: Kim D. Anderson, M. Morin, Andrea Beckel-mitchener, Charlotte D. Mobarak, Rachael L. Neve, Henry Furneaux, Richard W. Burry, Nora I. Perrone-bizzozeroAbstract:We have previously shown that the RNA-binding Protein HuD binds to a regulatory element in the growth-associated Protein (GAP)-43 mRNA and that this interaction involves its first two RNA recognition motifs (RRMs). In this study, we investigated the functional significance of this interaction by overexpression of human HuD Protein (pcHuD) or its truncated form lacking the third RRM (pcHuD I+II) in PC12 cells. Morphological analysis revealed that pcHuD cells extended short neurites containing Gap-43-positive growth cones in the absence of nerve growth factor (NGF). These processes also contained tubulin and F-actin filaments but were not stained with antibodies against neurofilament M Protein. In correlation with this phenotype, pcHuD cells contained higher levels of Gap-43 without changes in levels of other NGF-induced Proteins, such as SNAP-25 and tau. In mRNA decay studies, HuD stabilized the Gap-43 mRNA, whereas HuD I+II did not have any effect either on Gap-43 mRNA stability or on the levels of Gap-43 Protein. Likewise, pcHuD I+II cells showed no spontaneous neurite outgrowth and deficient outgrowth in response to NGF. Our results indicate that HuD is sufficient to increase Gap-43 gene expression and neurite outgrowth in the absence of NGF and that the third RRM in the Protein is critical for this function.
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the rna binding Protein hud is required for gap 43 mrna stability gap 43 gene expression and pkc dependent neurite outgrowth in pc12 cells
Molecular Biology of the Cell, 2000Co-Authors: Charlotte D. Mobarak, Kim D. Anderson, M. Morin, Henry Furneaux, Andrea Beckelmitchener, Sherry L Rogers, Peter H King, Nora I PerronebizzozeroAbstract:The RNA-binding Protein HuD binds to a regulatory element in the 39 untranslated region (39 UTR) of the Gap-43 mRNA. To investigate the functional significance of this interaction, we generated PC12 cell lines in which HuD levels were controlled by transfection with either antisense (pDuH) or sense (pcHuD) constructs. pDuH-transfected cells contained reduced amounts of Gap-43 Protein and mRNA, and these levels remained low even after nerve growth factor (NGF) stimulation, a treatment that is normally associated with Protein kinase C (PKC)dependent stabilization of the Gap-43 mRNA and neuronal differentiation. Analysis of Gap-43 mRNA stability demonstrated that the mRNA had a shorter half-life in these cells. In agreement with their deficient Gap-43 expression, pDuH cells failed to grow neurites in the presence of NGF or phorbol esters. These cells, however, exhibited normal neurite outgrowth when exposed to dibutyryl-cAMP, an agent that induces outgrowth independently from Gap-43. We observed opposite effects in pcHuD-transfected cells. The Gap-43 mRNA was stabilized in these cells, leading to an increase in the levels of the Gap-43 mRNA and Protein. pcHuD cells were also found to grow short spontaneous neurites, a process that required the presence of Gap-43. In conclusion, our results suggest that HuD plays a critical role in PKC-mediated neurite outgrowth in PC12 cells and that this Protein does so primarily by promoting the stabilization of the Gap-43 mRNA.
