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Journal ArticleDOI

GAP-43 expression in the medulla of macaque monkeys: changes during postnatal development and the effects of early median nerve repair.

21 Dec 1995-Developmental Brain Research (Elsevier)-Vol. 90, Iss: 1, pp 24-34
TL;DR: The results suggest that reorganization mechanisms at central terminals of peripheral nerves are very different following prenatal than postnatal nerve damage.
About: This article is published in Developmental Brain Research.The article was published on 1995-12-21. It has received 7 citations till now. The article focuses on the topics: Macaque & Cuneate nucleus.
Citations
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Journal ArticleDOI
TL;DR: The assumption that congenital absence of a limb does not lead to cortical reorganization or phantom limbs is confirmed whereas traumatic amputations that are accompanied by phantom limb pain show shifts of the cortical areas adjacent to the amputation zone towards the representation of the deafferented body part.
Abstract: The extent of the cortical somatotopic map and its relationship to phantom phenomena was tested in five subjects with congenital absence of an upper limb, four traumatic amputees with phantom limb pain and five healthy controls. Cortical maps of the first and fifth digit of the intact hand, the lower lip and the first toe (bilaterally) were obtained using neuroelectric source imaging. The subjects with congenital upper limb atrophy showed symmetric positions of the left and right side of the lower lip and the first toe, whereas the traumatic amputees with pain showed a significant shift (about 2.4 cm) of the cortical representation of the lower lip towards the hand region contralateral to the amputation side but no shift for the toe representation. In healthy controls, no significant hemispheric differences between the cortical representation of the digits, lower lip or first toe were found. Phantom phenomena were absent in the congenital but extensive in the traumatic amputees. These data confirm the assumption that congenital absence of a limb does not lead to cortical reorganization or phantom limbs whereas traumatic amputations that are accompanied by phantom limb pain show shifts of the cortical areas adjacent to the amputation zone towards the representation of the deafferented body part.

142 citations

Journal ArticleDOI
02 May 1996-Nature
TL;DR: It is shown that there is little or no topographic order in the median nerve to the hand after median nerve section and surgical repair in immature macaque monkeys, and in the same animals the representation of the reinnervated hand in primary somato-sensory cortēx is quite orderly.
Abstract: Transection of a sensory nerve in adults results in profound abnormalities in sensory perception, even if the severed nerve is surgically repaired to facilitate accurate nerve regeneration. In marked contrast, fewer perceptual errors follow nerve transection and surgical repair in children. The basis for this superior recovery in children was unknown. Here we show that there is little or no topographic order in the median nerve to the hand after median nerve section and surgical repair in immature macaque monkeys. Remarkably, however, in the same animals the representation of the reinnervated hand in primary somatosensory cortex area (area 3b) is quite orderly. This indicates that there are mechanisms in the developing brain that can create cortical topography, despite disordered sensory inputs. Presumably the superior recovery of perceptual abilities after peripheral nerve transection in children depends on this restoration of somatotopy in the central sensory maps.

91 citations

Journal ArticleDOI
TL;DR: The combined results suggest that the early phase of regeneration of peripheral nerves in the presence of peptide‐incorporated collagen tubes results in the enhanced production of trophic factors by the recruited hematogenous cells and Schwann cells, which in turn help in the secretion of certain vital Trophic and tropic factors essential for early regeneration.
Abstract: Neurotrophic factors play an important modulatory role in axonal sprouting during nerve regeneration involving the proliferation of hematogenous and Schwann cells in damaged tissue. We have exposed lesioned sciatic nerves to a collagen prosthesis with covalently bonded small cell adhesive peptides Arg-Gly-Asp-Ser (RGDS), Lys-Arg-Asp-Ser (KRDS), and Gly-His-Lys (GHK) to study local production of growth factors and cytokines in the regenerating tissues. Western/enzyme-linked immunosorbent assay (ELISA) studies were performed after 10 days of regeneration, when the tubular prosthesis is filled with fibrous matrix infiltrated by hematogenous cells and proliferating Schwann cells with growth factors produced locally. Regeneration was also analyzed by morphometrical methods after 30 days. The quantification of growth factors and proteins by ELISA revealed that there was an enhanced expression of the neurotrophic factors nerve growth factor (NGF) and neurotrophins (NT-3 and NT-4) in the regenerating tissues. This was further established by Western blot to qualitatively analyze the presence of the antigens in the regenerating tissues. Schwann cells were localized in the regenerating tissues using antibodies against S-100 protein. Other growth factors including growth-associated protein 43 (GAP-43), apolipoprotein E (Apo E), and pro-inflammatory cytokine like interleukin-1alpha (IL-1alpha) expression in the peptide groups were evaluated by ELISA and confirmed by Western blotting. Cell adhesive integrins in the proliferating cells were localized using integrin-alpha V. The combined results suggest that the early phase of regeneration of peripheral nerves in the presence of peptide-incorporated collagen tubes results in the enhanced production of trophic factors by the recruited hematogenous cells and Schwann cells, which in turn help in the secretion of certain vital trophic and tropic factors essential for early regeneration. Furthermore, hematogenous cells recruited within the first 10 days of regeneration help in the production of inflammatory mediators like interleukins that in turn stimulate Schwann cells to produce NGF for axonal growth.

29 citations


Cites background from "GAP-43 expression in the medulla of..."

  • ...The expression of GAP-43, a neuronal-specific growth-associated phosphoprotein, has been highly correlated with the growth and remodeling of the nervous system during development and regeneration (Jain et al., 1995)....

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Journal ArticleDOI
TL;DR: GAP43 expression is involved in timing of muscle maturation in-vivo, and the emerging hypothesis indicates that GAP43 interacts with calmodulin to indirectly modulate the activities of dihydropyridine and ryanodine Ca2+ channels, from functional excitation-contraction coupling, to cell metabolism, and gene expression.
Abstract: Neuronal growth-associated protein 43 (GAP43) has crucial roles in the nervous system, and during development, regeneration after injury, and learning and memory. GAP43 is expressed in mouse skeletal muscle fibers and satellite cells, with suggested its involvement in intracellular Ca2+ handling. However, the physiological role of GAP43 in muscle remains unknown. Using a GAP43-knockout (GAP43-/-) mouse, we have defined the role of GAP43 in skeletal muscle. GAP43-/- mice showed low survival beyond weaning, reduced adult body weight, decreased muscle strength, and changed myofiber ultrastructure, with no significant differences in the expression of markers of satellite cell and myotube progression through the myogenic program. Thus GAP43 expression is involved in timing of muscle maturation in-vivo. Intracellular Ca2+ measurements in-vitro in myotubes revealed GAP43 involvement in Ca2+ handling. In the absence of GAP43 expression, the spontaneous Ca2+ variations had greater amplitudes and higher frequency. In GAP43-/- myotubes, also the intracellular Ca2+ variations induced by the activation of dihydropyridine and ryanodine Ca2+ channels, resulted modified. These evidences suggested dysregulation of Ca2+ homeostasis. The emerging hypothesis indicates that GAP43 interacts with calmodulin to indirectly modulate the activities of dihydropyridine and ryanodine Ca2+ channels. This thus influences intracellular Ca2+ dynamics and its related intracellular patterns, from functional excitation-contraction coupling, to cell metabolism, and gene expression.

16 citations


Cites background or result from "GAP-43 expression in the medulla of..."

  • ...The levels of GAP43 expression are critical not only for nervous system development and growth (Jain et al., 1995; Murata et al., 2005), but also for skeletal muscle development after birth....

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  • ...Furthermore, as other studies have also reported for specific areas of neuronal tissue (Jain et al., 1995; Murata et al., 2005), in the WT mice, from birth to old age, the GAP43 expression decreased whenmuscle maturation was complete (i.e., at 1 to 4 months old) and remained low during old age…...

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Journal ArticleDOI
TL;DR: The ability to adjust to changes in the external environment is critical for learning and for recovery from brain injury as discussed by the authors, and the ability to respond in a reliable way is crucial for learning.
Abstract: Two basic features of our brains seem almost incompatible with each other One feature is the processing of information in a predictable and reliable manner In order to do this, one would suppose that the machinery of the brain, the local circuits and processing pathways, would be morphologically and functionally stable, at least in adults Yet, the second feature-the ability to adjust to changes in the external environment-is critical for learning and for recovery from brain injury How can circuits change and yet allow us to respond in a reliable way? Many investigators resolved this quandary by assuming that although most circuits in the brain

9 citations

References
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Journal ArticleDOI
19 Aug 1983-Science
TL;DR: After median nerve fibers to glabrous skin on the hands of monkeys were crushed and allowed to regenerate, normal topographical organization was recovered in the representation of the hand in primary somatosensory cortex.
Abstract: After median nerve fibers to glabrous skin on the hands of monkeys were crushed and allowed to regenerate, normal topographical organization was recovered in the representation of the hand in primary somatosensory cortex. Similar recovery of normal cortical organization may underlie the sensory restoration that usually follows nerve crush injury in humans.

106 citations

Journal ArticleDOI
TL;DR: It is hypothesize that the increases in density and distribution of reactivity for the lectins and GAP-43, as well as the decreases in neuropeptide reactivity, reflect injury-induced regenerative changes in primary afferent terminals.

87 citations

Journal ArticleDOI
TL;DR: The signals that alter GAP-43 expression in unmyelinated and myelinated afferents after peripheral nerve injury appear to operate with different time-courses.

87 citations

Journal ArticleDOI
TL;DR: Data suggest the possibility that the native form of GAP/B‐50 in the presynaptic membrane may be a tetramer of four identical subunits, including its correct molecular weight and possible polymeric structure.
Abstract: The protein that has been identified in different contexts as growth-associated protein (GAP)-43, GAP-48, protein 4, B-50, F-1 gamma 5, and pp46, has been implicated in neural development, axonal regeneration, and the modulation of synaptic function. The present study investigated various properties of this protein (designated here as GAP/B-50), including its correct molecular weight and possible polymeric structure. GAP/B-50 was purified to greater than 90% homogeneity using an alkaline extraction procedure followed by a two-stage separation on a size-exclusion HPLC column. The equivalence of the purified protein to the B-50 phosphoprotein was confirmed by peptide digests, comigration, immunostaining, and amino acid composition. On a series of sodium dodecyl sulfate-polyacrylamide gels the apparent molecular weight of the protein was seen to vary inversely with the concentration of acrylamide in the gels. Using these data in the method of Ferguson, the molecular weight of GAP/B-50 was calculated to be 32.8 kilodaltons (kD), considerably lower than the previously reported values of 43-67 kD. The low molecular weight of the protein in the presence of detergent was confirmed by density centrifugation. In the absence of detergent, however, the protein was found to be part of a polymeric structure whose retention time by size-exclusion chromatography indicated a size of 124 kD; this property was also confirmed by density centrifugation under nondetergent conditions. These data suggest the possibility that the native form of GAP/B-50 in the presynaptic membrane may be a tetramer of four identical subunits.

78 citations

Journal ArticleDOI
TL;DR: It is found that the mRNA transcripts of the genes for the neuronal growth-associated protein GAP43, the type II calcium/calmodulin-dependent protein kinase, and glutamic acid decarboxylase are increased in the visual cortex of animals reared in the dark.
Abstract: We have examined the regulation of expression of the genes for the neuronal growth-associated protein GAP43, the type II calcium/calmodulin-dependent protein kinase, and glutamic acid decarboxylase in the kitten visual cortex during normal postnatal development and after a period of visual deprivation. We find that the mRNA transcripts of these genes display very different patterns of normal development but are all increased in the visual cortex of animals reared in the dark. Upon exposure to light, the transcript of the GAP43 gene drops to near-normal levels within 12 hr.

75 citations