Skip to main content
Log in

Reactive astrocytes in the kainic acid-damaged hippocampus have the phenotypic features of type-2 astrocytes

  • Published:
Journal of Neurocytology

Summary

Kainic acid treatment, a model of temporal lobe epilepsy, induces Ammon's horn sclerosis characterized by degeneration of CA3 pyramidal neurons and reactive gliosis. We now report that in kainic acid treated rats, reactive astrocytes in the hippocampus are A2B5 immunopositive and express GAP-43 immunoreactivity. A2B5 is a cell surface ganglioside selectively expressed in the glial O-2A lineage (oligodendrocytes and type-2 astrocytesin vitro). Since A2B5-positive cells were also GFAP immunoreactive, our observations suggest that hippocampal-reactive astrocytes in the epileptic process are type-2 astrocytes.

GAP-43 is a membrane-associated phosphoprotein involved in neurite outgrowth.In vitro analysis showed that the glial O-2A lineage may express this phosphoprotein. In this study, we found that GAP-43 was coexpressed in astrocytes with A2B5 suggesting thatin vivo asin vitro type-2 astrocytes express GAP-43.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Albe-Fessard, D., Stutinski, F. &Libouban-Le-Touze, S. (1971)Atlas stéréotaxique du diencephale du rat blanc. Paris: CNRS.

    Google Scholar 

  • Anderson, P.-B., Perry, V. H. &Gordon, S. (1991) The kinetics and morphological characteristics of the macrophage-microglial response to kainic acid-induced neuronal degeneration.Neuroscience 42, 201–14.

    PubMed  Google Scholar 

  • Baudier, J., Bronner, C., Kligman, D. &Cole, R. D. (1989) Protein kinase C substrates from bovine brain: purification and characterization of neuromodulin, a neuron-specific calmodulin-binding protein.Journal of Biological Chemistry 264, 1824–8.

    PubMed  Google Scholar 

  • Ben-Ari, Y. (1985) Limbic seizures and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy.Neuroscience 14, 375–403.

    PubMed  Google Scholar 

  • Ben-Ari, Y., Tremblay, E., Ottersen, O. P. &Naquet, R. (1979) Evidence suggesting secondary epileptogenic lesion after kainic acid: pretreatment with diazepam reduces distant but not local brain damage.Brain Research 165, 362–5.

    PubMed  Google Scholar 

  • Ben-Ari, Y., Tremblay, E. &Ottersen, O. P. (1980) Injection of kainic acid into the amygdaloid complex of the rat: an electrographic, clinical and histological study in relation to the pathology of the epilepsy.Neuroscience 5, 515–28.

    PubMed  Google Scholar 

  • Benowitz, L. I., Perrone-Bizzozero, N. I. &Finkle-Stein, S. P. (1987) Molecular properties of the growth-associated protein GAP-43 (B-50).Journal of Neurochemistry 48, 1640–7.

    PubMed  Google Scholar 

  • Biffo, S., Verhaagen, J., Schrama, L. H., Schotman, P., Danho, W. &Margolis, F. L. (1990) B-50/GAP-43 expression correlates with process outgrowth in the embryonic mouse nervous system.European Journal of Neuroscience 2, 487–99.

    PubMed  Google Scholar 

  • Crépel, V., Represa, A., Beaudoin, M. &Ben-Ari, Y. (1989) Hippocampal damage induced by ischemia and intra-amygdaloid kainate injection: effects on NMDA, TCP and glycine binding sites.Neuroscience 31, 605–12.

    PubMed  Google Scholar 

  • Curtis, R., Hardy, R., Reynolds, R., Spruce, B. A. &Wilkin, G. P. (1991) Down-regulation of GAP-43 during oligodendrocyte development and lack of expression by astrocytesin vivo: implications for macroglial differentiation.European Journal of Neuroscience 3, 876–86.

    PubMed  Google Scholar 

  • David, S., Miller, R. H., Patel, R. &Raff, M. C. (1984) Effects of neonatal transection on glial cell development in the rat optic nerve: evidence that the oligodendrocyte-type 2 astrocyte cell lineage depends on axons for its survival.Journal of Neurocytology 13, 961–74.

    PubMed  Google Scholar 

  • Deloulme, J. C., Janet, T., Au, D., Storm, D. R., Sensen-Brenner, M. &Baudier, J. (1990) Neuromodulin (GAP43): a neuronal protein kinase C substrate is also present in 0–2A glial cell lineage. Characterization of neuromodulin in secondary cultures of oligodendrocytes and comparison with the neuronal antigen.Journal of Cell Biology 111, 1559–69.

    PubMed  Google Scholar 

  • Dubois-Dalcq, M. (1987) Characterization of a slowly proliferative cell along the oligodendrocyte pathway.EMBO Journal 6, 2587–95.

    PubMed  Google Scholar 

  • Dusart, I., Marty, S. &Peschanski, M. (1991) Glial changes following an excitotoxic lesion in the CNS-II. Astrocytes.Neuroscience 45, 541–9.

    PubMed  Google Scholar 

  • Godfraind, C., Friedrich, V. L., Holmes, K. V. &Dubois-Dalcq, M. (1989)In vivo analysis of glial cell phenotypes during a viral demyelinating disease in mice.Journal of Cell Biology 109, 2405–16.

    PubMed  Google Scholar 

  • Goslin, K., Schreyer, D. J., Skene, J. H. P. &Banker, G. (1988) Development of neuronal polarity: GAP-43 distinguishes axonal from dendritic growth cones.Nature 336, 672–4.

    PubMed  Google Scholar 

  • Jacobson, R. D., Virag, I. &Skene, J. H. P. (1986) A protein associated with axon growth, GAP-43 is widely distributed and developmentally regulated in rat CNS.Journal of Neuroscience 6, 1843–55.

    Google Scholar 

  • Laemmli, U. K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4.Nature 227, 680–5.

    PubMed  Google Scholar 

  • Levine, S. M., Seyfried, T. N., Yu, R. K. &Goldman, J. E. (1986) Immunocytochemical localization of GD3 ganglio-side to astrocytes in murine cerebellar mutants.Brain Research 374, 260–9.

    PubMed  Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L. &Randall, R. J. (1951) Protein measurement with the folin phenol reagent.Journal of Biological Chemistry 193, 265–72.

    PubMed  Google Scholar 

  • Marty, S., Dusart, I. &Peschanski, M. (1991) Glial changes following an excitotoxic lesion in the CNS-I. Microglia/macrophages.Neuroscience 45, 529–39.

    PubMed  Google Scholar 

  • McGuire, C. B., Snipes, G. J. &Norden, J. J. (1988) Light-microscopic immunolocalization of the growth- and plasticity-associated protein GAP-43 in the developing rat brain.Developmental Brain Research 41, 277–91.

    Google Scholar 

  • Meiri, K. F. &Gordon-Weeks, P. R. (1990) 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.Journal of Neuroscience 10, 256–66.

    Google Scholar 

  • Miller, R. H., David, S., Patel, R., Abney, E. R. &Raff, M. C. (1985) A quantitative immunohistochemical study of macroglial cell development in the rat optic nerve:in vivo evidence for two distinct astrocyte lineages.Developmental Biology 111, 35–41.

    PubMed  Google Scholar 

  • Moss, D. J., Fernyhough, P., Chapman, K., Baizer, L., Bray, D. &Allsopp, T. (1990) Chicken growth-associated protein GAP-43 is tightly bound to the actinrich neuronal membrane skeleton.Journal of Neurochemistry 54, 729–36.

    PubMed  Google Scholar 

  • Nadler, J. V., Perry, B. W., Gentry, C. &Cotman, C. W. (1980) Loss and reacquisition of hippocampal synapses after selective destruction of CA3-CA4 afferents with kainic acid.Brain Research 191, 387–403.

    PubMed  Google Scholar 

  • Neve, R. L., Perrone-Bizzozero, N. I., Finklestein, S., Zwiers, H., Bird, E., Kurnit, D. M. &Benowitz, L. I. (1987) The neuronal growth-associated protein GAP-43 (B50, F1): neuronal specificity, developmental regulation and regional distribution of the human and rat mRNAs.Molecular Brain Research 2, 177–83.

    Google Scholar 

  • Oestreicher, A. B. &Gispen, W. H. (1986) Comparison of the immunocytochemical distribution of the phospho-protein B-50 in the cerebellum and hippocampus of immature and adult rat brain.Brain Research 375, 267–79.

    PubMed  Google Scholar 

  • Okazaki, M. M. &Nadler, J. V. (1988) Protective effects of mossy fiber lesions against kainic acid-induced seizures and neuronal degeneration.Neuroscience 26, 763–81.

    PubMed  Google Scholar 

  • Raff, M. C. (1989) Glial cell diversification in the rat optic nerve.Science 243, 1450–5.

    PubMed  Google Scholar 

  • Raff, M. C., Miller, R. H. &Noble, M. (1983) A glial progenitor cell that developsin vitro into astrocyte or an oligodendrocyte depending on culture medium.Nature 303, 390–6.

    PubMed  Google Scholar 

  • Represa, A., Tremblay, E. &Ben-Ari, Y. (1987) Kainate binding sites in the hippocampal mossy fibers: localization and plasticity.Neuroscience 20, 739–48.

    PubMed  Google Scholar 

  • Shea, T. B., Perrone-Bizzozero, N. I., Beermann, M. L. &Benowitz, L. I. (1991) Phospholipid-mediated delivery of anti-GAP-43 antibodies into neuroblastoma cells prevents neuritogenesis.Journal of Neuroscience 11, 1685–90.

    Google Scholar 

  • Skene, J. H. P. (1989) Axonal growth-associated proteins.Annual Review of Neuroscience 12, 127–56.

    PubMed  Google Scholar 

  • Tauck, D. L. &Nadler, J. V. (1985) Evidence for functional mossy fiber sprouting in hippocampal formation of kainic acid treated rats.Journal of Neuroscience 5, 1016–22.

    PubMed  Google Scholar 

  • Van Lookeren Campagne, M., Oestreicher, A. B., Van Bergen En Henegouwen, P. M. P. &Gispen, W. H. (1990) Ultrastructural double localization of B50/GAP-43 and synaptophysin (p38) in the neonatal and adult rat hippocampus.Journal of Neurocytology 19, 948–61.

    PubMed  Google Scholar 

  • Vayssen, P. J.-J. &Goldman, J. E. (1992) A distinct type of GD3+, flat astrocyte in rat CNS cultures.Journal of Neuroscience 12, 330–70.

    PubMed  Google Scholar 

  • Vitkovic, L., Steisslinger, H. W., Aloyo, V. J. &Mersel, M. (1988) The 43-kDa neuronal growth-associated protein (GAP-43) is present in plasma membranes of rat astrocytes.Proceedings of the National Academy of Sciences (USA) 85, 8296–300.

    Google Scholar 

  • Yamamoto, M., Marshall, P., Hemmendinger, L. M., Boyer, A. B. &Caviness, V. S. Jr. (1988) Distribution of glucuronic acid- and -sulfate-containing glycoproteins in the central nervous system of the adult mouse.Neuroscience Research 5, 273–98.

    PubMed  Google Scholar 

  • Zuber, M. X., Goodman, D. W., Karns, L. R. &Fishman, M. C. (1989) The neuronal growth-associated protein GAP-43 induces filopodia in non-neuronal cells.Science 244, 1193–5.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Represa, A., Niquet, J., Charriaut-Marlangue, C. et al. Reactive astrocytes in the kainic acid-damaged hippocampus have the phenotypic features of type-2 astrocytes. J Neurocytol 22, 299–310 (1993). https://doi.org/10.1007/BF01187128

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01187128

Keywords

Navigation