1,852 research outputs found

    Live or let die – retinal ganglion cell death and survival during development and in the lesioned adult CNS

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    Programmed cell death or apoptosis is a common and widespread phenomenon that is important for proper development of the nervous system. In the adult CNS, however, apoptosis contributes to secondary cell loss after various types of lesions. The retino-tectal system has been successfully used as a convenient model system to study the molecular mechanisms of neuronal apoptosis and survival during development and in the lesioned adult CNS. This review describes the current knowledge about the interactions of cell death and survival pathways in general and for retinal ganglion cells specifically

    Adult rat retinal glia in vitro: effects of in vivo crush-activation on glia proliferation and permissiveness for regenerating retinal ganglion cell axons

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    The effects of optic nerve crush on adult rat retinal glia activation were studied in vitro. In adult rats the optic nerves were crushed and the corresponding retinae were explained 5 to 7 days later and cultured in vitro. The glial response of retinae with precrushed optic nerves was compared to the glial response of retinae without prior optic nerve crush. As a consequence of crush-axotomy more glial cells migrated out from retinal explants and covered significantly larger areas of the substratum than glia from noncrushed retinae. Migration of immunohistochemically distinguishable Vimentin-positive Müller cells and glial fibrillary acidic protein-positive astrocytes could be observed in both types of cultures. Astrocytes as well as Müller cells incorporated bromodeoxyuridine after explantation. In noncrushed retinal explants Thy 1.1-immunopositive flat cells were much more frequent and the relative proportion of glial cells was much lower than in crush-activated cultures. In a second set of experiments the ability of adult rat retinal glia to support retinal ganglion cell regeneration was examined. Normal retinal explants (without optic nerve crush) which usually do not substantially regenerate axons were cultured on retinal glia from normal and crush-activated explants. Both glia preparations supported axon growth from retinal explants after 3 days in vitro. Neuritic growth was significantly better when retinal explants from normal adult rats were cultured on crush-activated retinal glia as compared to glia derived from noncrushed retinae. It is concluded that activated adult rat retinal glia, unlike adult glia found in other brain regions, support adult rat retinal ganglion cell regeneration in vitro

    Myelin from peripheral and central nervous system is a nonpermissive substrate for retinal ganglion cell axons

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    In the CNS of mammals axonal regeneration is limited by inhibitory influences of the glial and extracellular environment. Myelin-associated inhibitors of neurite growth as well as some properties of so called "reactive astrocytes" which make the environment nonpermissive for axonal growth contribute to the inhibitory nature of the mammalian CNS. In contrast, the PNS is supportive of regeneration and Schwann cell surfaces and Schwann-cell-derived extracellular matrix provide suitable substrates for regenerating axons in vivo and in vitro. However, as the results presented here indicate, myelin derived from normal and axotomized sciatic nerves is a nonpermissive substrate for axonal regrowth. Addition of laminin to either CNS or PNS myelin or freezing of the myelin, however, allows reproducibly axonal growth. Membrane preparations from CNS or PNS tissue on the other hand allow axon outgrowth from retinal explants when adhesive substrates (e.g., polylysin) are available. This suggests that inhibitors of neurite growth are present in myelin from the CNS and PNS. Growth supportive substrates, which are present in large quantities after PNS but not after CNS injury, can overcome nonpermissive substrate properties

    Retinal ganglion cell axons recognize specific guidance cues present in the deafferented adult rat superior colliculus

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    During development, retinal ganglion cell axons establish a topographically ordered projection from the retina to the superior colliculus (SC). The putative guidance activities for retinal axons that operate during embryonic development are not detectable in the normal adult SC. However, these cues reappear upon transection of the optic nerve of adult rats. In the present study, we used a modified version of the 'stripe assay,' in which membranes from either anterior or posterior SC alternated with laminin stripes. Temporal embryonic retinal axons consistently avoid membranes from embryonic posterior SC, but only rarely from adult deafferented SC. However, they are attracted to membranes from both embryonic and adult deafferented anterior SC. Nasal retinal axons only show a significant preference for membranes from posterior SC after deafferentation. When retinal axons were offered a choice to grow on membranes either from their embryonic or their deafferented target regions, they showed a preference for the deafferented SC. On carpets consisting of laminin and membranes from normal SC (not deafferented) or nontarget regions (inferior colliculus), temporal and nasal axons grow either in a random fashion or show preferences for the laminin stripes. Our modified version of the classic stripe assay shows specific growth preferences of embryonic retinal axons for membrane lanes from their appropriate embryonic or deafferented adult target regions. These findings suggest that the deafferentation of the SC in adult rats triggers the reexpression of specific guidance activities for retinal axons. Those 'attractive' guidance cues appear to be differentially expressed in the developing and deafferented SC

    Is there a role of Tau in Huntington's disease?

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    Alterations of the cerebrospinal fluid (CSF) composition are useful clinical diagnostic tools as well as a source of candidates for new biomarkers of neurodegenerative disorders. This Editorial highlights a study by Rodrigues and colleagues in which the authors try to establish Tau as a new biomarker for Huntingtons disease (HD). The study confirmed in two independent, age-controlled patient populations at various disease stages, asymptomatic mutation carriers and healthy controls, that CSF total Tau concentrations in HD gene mutation carriers are increased compared with healthy controls. This is a strong evidence that CSF total Tau concentration is associated with phenotypic variability in HD. Read the highlighted article Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease' on page . Alterations of the cerebrospinal fluid (CSF) composition are useful clinical diagnostic tools as well as a source of candidates for new biomarkers of neurodegenerative disorders. This Editorial highlights a study by Rodrigues and colleagues in which the authors try to establish Tau as a new biomarker for Huntington ' s disease (HD). The study confirmed in two independent, age-controlled patient populations at various disease stages, asymptomatic mutation carriers and healthy controls, that CSF total Tau concentrations in HD gene mutation carriers are increased compared with healthy controls. This is a strong evidence that CSF total Tau concentration is associated with phenotypic variability in HD. Read the highlighted article Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease' on page

    Growth promoting and inhibitory effects of glial cells in the mammalian nervous system

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    In the central nervous sytem (CNS) of mammals axonal regeneration is limited by two main factors: first, the low intrinsic regenerative potential of adult CNS neurons and second, inhibitory influences of the glial and extracellular environment. Myelin-associated inhibitors of neurite growth as well as some properties of so called "reactive astrocytes" contribute to the non-permissive of CNS tissue for axonal growth. In contrast, the peripheral nervous system (PNS) environment is supportive of regeneration because Schwann cells provide suitable substrates for regrowing axons. Purified PNS myelin, however, inhibits growth of PNS and CNS axons to a similar extent as does CNS myelin. The molecular basis of glial substrate properties has been studied intensively in the recent years and a large number of molecules have been recognized which might play a role in the regulation of axonal growth. Although the exact mechanisms are still not fully understood, accumulating data shed light on the complex interactions between neurons and glia that are required to establish, maintain, and regenerate axonal connections in the nervous system. In the following chapter we review the role of glial cells in the CNS and PNS during processes of de- and regeneration with respect to our own work

    Reactive changes of glial cells after optic nerve axotomy in adult rats

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    We have studied the glial response to optic nerve axotomy in vitro. Glial cells were obtained from normal and crush-axotomized optic nerves. In cultures from axotomized nerves, large numbers of astrocytes, oligodendrocyte progenitors and mature oligodendrocytes were found. Significantly fewer astrocytes and oligodendrocyte progenitors were present in cultures from normal nerves, mature oligodendrocytes did not occur. Proliferation and maturation of oligodendrocyte progenitor cells was only observed in cultures from axotomized nerves, suggesting the regulatory influence of blood-derived factors which are not present in normal nerves after in vitro axotomy. These data show that optic nerve injury enhances the ability of astrocytes, oligodendrocytes and their precursors to survive and/or proliferate in vitro
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