Inverse patterns of myelination and GAP‐43 expression in the adult CNS: Neurite growth inhibitors as regulators of neuronal plasticity?

In the central nervous system (CNS) myelin is present not only in white matter, but also in varying amounts in many gray matter areas. In addition to the function of electrical insulation of axons, myelin and oligodendrocytes contain molecules that are powerful inhibitors of neurite growth. Nevertheless plastic changes involving sprouting of nerve terminals occur in several brain regions of adult animals after partial lesions. In this study we have tried to correlate the plastic potential of CNS regions with the degree of their myelination. The expression of the growth‐associated protein GAP‐43 was used as an indicator of the potential for plastic changes, and a histological myelin stain was used to assess myelination. We have found that myelination and GAP‐43 expression have strikingly inverse expression patterns in the majority of CNS gray matter areas. Densely myelinated regions, that is, most brainstem nuclei, the tegmentum, and the inferior colliculus, are low in GAP‐43. In contrast, unmyelinated or lightly myelinated areas, such as the substantia gelatinosa of the spinal cord, the nucleus of the solitary tract, or the septum, express high levels of GAP‐43. Areas known to show lesion‐induced sprouting are typically high in GAP‐43 and only lightly myelinated. During postnatal development the myelination pattern precedes the GAP‐43 pattern, a sequence that is consistent with a role of myelin and the associated neurite growth inhibitors in modifying GAP‐43 expression.

[1]  M. Fishman,et al.  GAP-43 as a plasticity protein in neuronal form and repair. , 1992, Journal of neurobiology.

[2]  M. Schwab,et al.  Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors , 1990, Nature.

[3]  D. Storm,et al.  Identification and characterization of the calmodulin-binding domain of neuromodulin, a neurospecific calmodulin-binding protein. , 1988, The Journal of biological chemistry.

[4]  J. Schwob,et al.  Monoclonal antibodies show that kinase C phosphorylation of GAP-43 during axonogenesis is both spatially and temporally restricted in vivo , 1991, The Journal of cell biology.

[5]  L. Benowitz,et al.  Mapping the development of the rat brain by GAP-43 immunocytochemistry , 1991, Neuroscience.

[6]  G. Recanzone,et al.  Topographic reorganization of the hand representation in cortical area 3b owl monkeys trained in a frequency-discrimination task. , 1992, Journal of neurophysiology.

[7]  C. Bandtlow,et al.  Oligodendrocytes arrest neurite growth by contact inhibition , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  J. Skene,et al.  Axonally transported proteins associated with axon growth in rabbit central and peripheral nervous systems , 1981, The Journal of cell biology.

[9]  T. Allsopp,et al.  A developmentally regulated chicken neuronal protein associated with the cortical cytoskeleton , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  M. Schwab,et al.  Codistribution of neurite growth inhibitors and oligodendrocytes in rat CNS: appearance follows nerve fiber growth and precedes myelination. , 1989, Developmental biology.

[11]  W. Gispen,et al.  Comparison of the immunocytochemical distribution of the phosphoprotein B-50 in the cerebellum and hippocampus of immature and adult rat brain , 1986, Brain Research.

[12]  Leyla deToledo-Morrell,et al.  Induction of long-term potentiation is associated with an increase in the number of axospinous synapses with segmented postsynaptic densities , 1991, Brain Research.

[13]  W. Gispen,et al.  Inhibition of nerve growth factor-induced B-50/GAP-43 expression by antisense oligomers interferes with neurite outgrowth of PC12 cells. , 1992, Biochemical and biophysical research communications.

[14]  M. Fishman,et al.  The neuronal growth-associated protein GAP-43 induces filopodia in non-neuronal cells. , 1989, Science.

[15]  W. Gispen,et al.  Immunolocalization of B-50 (GAP-43) in the mouse olfactory bulb: Predominant presence in preterminal axons , 1992, Journal of neurocytology.

[16]  S. Rose,et al.  Training induced dendritic spine density changes are specifically related to memory formation processes in the chick, Gallus domesticus , 1988, Brain Research.

[17]  S. Jacobson Sequence of myelinization in the brain of the albino rat. A. Cerebral cortex, thalamus and related structures , 1963, The Journal of comparative neurology.

[18]  A. Routtenberg,et al.  Selective expression of protein F1/(GAP-43) mRNA in pyramidal but not granule cells of the hippocampus , 1991, Neuroscience.

[19]  S. Finklestein,et al.  Anatomical distribution of the growth-associated protein GAP-43/B-50 in the adult rat brain , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  D. Purves,et al.  Changes in the dendritic branching of adult mammalian neurones revealed by repeated imaging in situ , 1985, Nature.

[21]  J. Kapfhammer,et al.  Inhibitors of neurite growth. , 1993, Annual review of neuroscience.

[22]  Carl W. Cotman,et al.  Selective reinnervation of hippocampal area CA1 and the fascia dentata after destruction of CA3-CA4 afferents with kainic acid , 1980, Brain Research.

[23]  J. Cavazos,et al.  Synaptic reorganization in the hippocampus induced by abnormal functional activity. , 1988, Science.

[24]  M. Schwab,et al.  Channeling of developing rat corticospinal tract axons by myelin- associated neurite growth inhibitors , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  E. Neer,et al.  G0 is a major growth cone protein subject to regulation by GAP-43 , 1990, Nature.

[26]  D. Bray,et al.  Chicken Growth‐Associated Protein GAP‐43 Is Tightly Bound to the Actin‐Rich Neuronal Membrane Skeleton , 1990, Journal of neurochemistry.

[27]  W. Gispen,et al.  Immunocytochemical distribution of the protein kinase C substrate B-50 (GAP43) in developing rat pyramidal tract , 1987, Neuroscience Letters.

[28]  R. Oppenheim,et al.  Anatomical and functional recovery following spinal cord transection in the chick embryo. , 1990, Journal of neurobiology.

[29]  D. Purves,et al.  Dynamic changes in the dendritic geometry of individual neurons visualized over periods of up to three months in the superior cervical ganglion of living mice , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  G. Vrensen,et al.  Changes in size and shape of synaptic connections after visual training: An ultrastructural approach of synaptic plasticity , 1981, Brain Research.

[31]  K. Kalil,et al.  A light and electron microscopic study of regrowing pyramidal tract fibers , 1982, The Journal of comparative neurology.

[32]  N. Perrone-Bizzozero,et al.  The expression of GAP-43 in relation to neuronal growth and plasticity: when, where, how, and why? , 1991, Progress in brain research.

[33]  R. Neve,et al.  The pattern of GAP-43 immunostaining changes in the rat hippocampal formation during reactive synaptogenesis. , 1990, Brain research. Molecular brain research.

[34]  P. Gordon-Weeks,et al.  GAP-43 in growth cones is associated with areas of membrane that are tightly bound to substrate and is a component of a membrane skeleton subcellular fraction , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  D. Schreyer,et al.  Fate of GAP-43 in ascending spinal axons of DRG neurons after peripheral nerve injury: delayed accumulation and correlation with regenerative potential , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  M. DiFiglia,et al.  Immunoreactive GAP‐43 in the neuropil of adult rat neostriatum: Localization in unmyelinated fibers, axon terminals, and dendritic spines , 1990, The Journal of comparative neurology.

[37]  C. Bendotti,et al.  Distribution of GAP‐43 mRNA in the adult rat brain , 1993, The Journal of comparative neurology.

[38]  P. Caroni,et al.  Phosphorylation-site mutagenesis of the growth-associated protein GAP- 43 modulates its effects on cell spreading and morphology , 1993, The Journal of cell biology.

[39]  J. Norden,et al.  Light-microscopic immunolocalization of the growth- and plasticity-associated protein GAP-43 in the developing rat brain. , 1988, Brain research.

[40]  E. J. Green,et al.  Effects of complex or isolated environments on cortical dendrites of middle-aged rats , 1983, Brain Research.

[41]  J. Priestley,et al.  The distribution of GAP-43 in normal rat spinal cord , 1993, Journal of neurocytology.

[42]  J. Kapfhammer,et al.  Modulators of neuronal migration and neurite growth. , 1992 .

[43]  P. Strata,et al.  Reinnervation of cerebellar Purkinje cells by climbing fibres surviving a subtotal lesion of the inferior olive in the adult rat. I. Development of new collateral branches and terminal plexuses , 1991, The Journal of comparative neurology.

[44]  J. Steeves,et al.  Axonal regeneration contributes to repair of injured brainstem-spinal neurons in embryonic chick , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[45]  G. Banker,et al.  Development of neuronal polarity: GAP-43 distinguishes axonal from dendritic growth cones , 1988, Nature.

[46]  F. Gallyas Silver staining of myelin by means of physical development. , 1979, Neurological research.

[47]  S. McMahon,et al.  Sprouting of peripherally regenerating primary sensory neurones in the adult central nervous system , 1991, The Journal of comparative neurology.

[48]  G. Schneider,et al.  Antibody neutralization of neurite growth inhibitors from oligodendrocytes results in expanded pattern of postnatally sprouting retinocollicular axons , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[49]  P. Caroni,et al.  Antibody against myelin associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter , 1988, Neuron.

[50]  G. Schneider,et al.  Immunohistochemical localization of GAP‐43 in the developing hamster retinofugal pathway , 1989, The Journal of comparative neurology.

[51]  M. Schwab,et al.  Regeneration of Lesioned Septohippocampal Acetylcholinesterase‐positive Axons is Improved by Antibodies Against the Myelin‐associated Neurite Growth Inhibitors NI‐35/250 , 1991, The European journal of neuroscience.

[52]  A. Björklund,et al.  Reformation of long axon pathways in adult rat central nervous system by human forebrain neuroblasts , 1990, Nature.

[53]  F. Morrell,et al.  Increase in the number of axospinous synapses with segmented postsynaptic densities following hippocampal kindling , 1992, Brain Research.

[54]  L. Benowitz,et al.  The growth-associated protein gap-43 appears in dorsal root ganglion cells and in the dorsal horn of the rat spinal cord following peripheral nerve injury , 1990, Neuroscience.

[55]  A. Lozano,et al.  Expression of the growth-associated protein GAP-43 in adult rat retinal ganglion cells following axon injury , 1991, Neuron.

[56]  W. Tetzlaff,et al.  Response of facial and rubrospinal neurons to axotomy: changes in mRNA expression for cytoskeletal proteins and GAP-43 , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[57]  J. Kaas,et al.  Reorganization of mammalian somatosensory cortex following peripheral nerve injury , 1982, Trends in Neurosciences.

[58]  M. Devor,et al.  Neuroplasticity in the rearrangement of olfactory tract fibers after neonatal transection in hamsters , 1976, The Journal of comparative neurology.

[59]  L. Benowitz,et al.  Increased transport of 44,000- to 49,000-dalton acidic proteins during regeneration of the goldfish optic nerve: a two-dimensional gel analysis , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[60]  L. Benowitz,et al.  GAP-43 expression in the developing rat lumbar spinal cord , 1991, Neuroscience.

[61]  E. Baetge,et al.  Neurite outgrowth in PC12 cells deficient in GAP-43 , 1991, Neuron.

[62]  B. K. Hartman,et al.  PURIFICATION AND IMMUNOHISTOCHEMICAL LOCALIZATION OF RAT BRAIN MYELIN PROTEOLIPID PROTEIN 1 , 1977, Journal of neurochemistry.

[63]  R. Burry,et al.  GAP-43 distribution is correlated with development of growth cones and presynaptic terminals , 1992, Journal of neurocytology.

[64]  N. Perrone-Bizzozero,et al.  Phospholipid-mediated delivery of anti-GAP-43 antibodies into neuroblastoma cells prevents neuritogenesis , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[65]  Dale Purves,et al.  Trophic regulation of nerve cell morphology and innervation in the autonomic nervous system , 1988, Nature.

[66]  Fred H. Gage,et al.  Reactive synaptogenesis assessed by synaptophysin immunoreactivity is associated with GAP-43 in the dentate gyrus of the adult rat , 1991, Experimental Neurology.

[67]  D. Purves,et al.  Postnatal construction of neural circuitry in the mouse olfactory bulb , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[68]  M. Mishkin,et al.  Massive cortical reorganization after sensory deafferentation in adult macaques. , 1991, Science.

[69]  G. Golarai,et al.  Mossy fiber synaptic reorganization induced by kindling: time course of development, progression, and permanence , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[70]  M. Schwab,et al.  Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading , 1988, The Journal of cell biology.

[71]  K. Meiri,et al.  Nerve growth factor stimulation of GAP-43 phosphorylation in intact isolated growth cones , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[72]  E. Kinnman,et al.  Expansion of spinal cord primary sensory afferent projection following combined sciatic nerve resection and saphenous nerve crush: A horseradish peroxidase study in the adult rat , 1988, The Journal of comparative neurology.

[73]  G. Wilkin,et al.  Up-regulation of GAP-43 and growth of axons in rat spinal cord after compression injury , 1993, Journal of neurocytology.

[74]  G. Schneider,et al.  Lesions of the brachium of the superior colliculus in neonate hamsters: Correlation of anatomy with behavior , 1981, Experimental Neurology.

[75]  G. Raisman,et al.  Long Fibre Growth by Axons of Embryonic Mouse Hippocampal Neurons Microtransplanted into the Adult Rat Fimbria , 1993, The European journal of neuroscience.

[76]  L. Dekker,et al.  Inhibition of noradrenaline release by antibodies to B-50 (GAP-43) , 1989, Nature.

[77]  M Holmes,et al.  Endogenous NGF and nerve impulses regulate the collateral sprouting of sensory axons in the skin of the adult rat , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[78]  R. Coggeshall,et al.  Peripheral nerve injury triggers central sprouting of myelinated afferents , 1992, Nature.