Skip to main content
Log in

Glial fibrillary acidic protein and RNA expression in adult rat hippocampus following low-level lead exposure during development

  • Original Paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

The astroglial cytoskeletal element, glial fibrillary acidie protein (GFAP), is a generally accepted sensitive indicator for neurotoxic effects in the mature brain. We used GFAP as a marker for structural changes in rat hippocampus related to chronic low level lead exposure during different developmental periods. Four groups of rats were investigated: a control group, a perinatal group, which was exposed during brain development (EO-P16), a permanent group, exposed during and after brain development (E0-P100), and a postweaning group, exposed after brain development (P16–P100). Sections were processed for light microscopy (hematoxylin-eosin, Nissl, periodic acid Schiff (PAS) and GFAP-specific immunohistology), for electron microscopy, and for in-situ hybridization (GFAP). Sections were prepared from animals tested for active avoidance learning (AAL) and long-term potentiation (LTP). Chronic lead exposure did not affect glial and neuronal functions, as assessed by LTP and AAL, when lead exposure started after brain development (postweaning group). In this group, astrocytes displayed increased GFAP and GFAP gene transcript levels. However, lead exposure affected neuronal and glial function when the intoxication fell into the developmental period of the brain (perinatal and permanent groups). In these groups, LTP and AAL were impaired, and astrocytes failed to react to the toxic exposure with an adequate increase of GFAP and GFAP gene transcripts. Although GFAP is an accepted marker for neurotoxicity, our data suggest the marker function of GFAP to be restricted to postnatal toxic insult.

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

  • Agency for Toxic Substances and Disease Registry (1988) The nature and extent of lead poisoning in children in the United States: a report to Congress US Department of Health and Human Services, Public Health Service. Atlanta

  • Alexander FW (1974) The uptake of lead by children in differing environments. Environ Health Perspect 7:155–159

    PubMed  Google Scholar 

  • Alkon DL, Amaral DG, Bear MF, Black J, Carew TJ, Cohen NJ, Disterhoft JF, Eichenbaum H, Golski S, Gorman J K et al. (1991) Learning and memory. FESN Study Group. Brain Res Rev 16:193–220

    PubMed  Google Scholar 

  • Altmann L, Sveinsson K, Wiegand H (1991) Long-term potentiation in rat hippocampal slices is impaired following acute lead perfusion. Neurosci Lett 128:109–112

    PubMed  Google Scholar 

  • Altmann L, Weinsberg F, Sveinsson K, Lilienthal H, Wiegand H, Winneke G (1993) Impairment of long-term potentiation and learning following chronic lead exposure. Toxicol Lett 66:105–112

    PubMed  Google Scholar 

  • Angell NF, Weiss B (1982) Operant behavior of rats exposed to lead before or after weaning. Toxicol Appl Pharmacol 63:62–71

    PubMed  Google Scholar 

  • Angevine JB (1975) Development of the hippocampal region. In: Isaacson RL, Pribram KH (eds) The hippocampus. Plenum Press, New York, pp 61–94

    Google Scholar 

  • Aquino DA, Chiu FC, Brosnan CF, Norton WT (1988) Glial fibrillary acidie protein increases in the spinal cord of Lewis rats with acute experimental autoimmune encephalomyelitis. J Neurochem 51:1085–1096

    PubMed  Google Scholar 

  • Averill DR, Needleman HL (1980) Neonatal lead exposure retards cortical synaptogenesis in the rat. In: Needleman HL (ed) Low level lead exposure. The clinical implications of current research. Raven Press. New York, pp 201–210

    Google Scholar 

  • Balaban CD, O'Callaghan JP, Billingsley ML (1988) Trimethyltin-induced neuronal damage in the rat brain: comparative studies using silver degeneration stains, immunohistochemistry and immunoassay for neuronotypic and gliotypic proteins. Neuroscience 26:337–361

    PubMed  Google Scholar 

  • Bayer SA (1980a) Development of the hippocampal region in the rat. I. Neurogenesis examined with 3H-thymidine autoradiography. J Comp Neurol 190:87–114

    PubMed  Google Scholar 

  • Bayer SA (1980b) Development of the hippocampal region in the rat. II. Morphogenesis during embryonic and early postnatal life. J Comp Neurol 190:115–134

    PubMed  Google Scholar 

  • Benjamin AM (1983) Ammonia in metabolic relations between neurons and glia. In: Hertz L, Kvanne E, McGeer EG, Schousboe A (eds) Glutamine, glutamate and GABA in the central nervous system. Liss, New York, pp 399–414

    Google Scholar 

  • Bignami A, Dahl D (1974) Astrocyte-specific protein and radial glia in the cerebral cortex of newborn rat. Nature 252:55–56

    PubMed  Google Scholar 

  • Bignami A, Eng LF, Dahl D, Uyeda CT (1972) Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Res 43:429–435

    PubMed  Google Scholar 

  • Brock TO, O'Callaghan JP (1987) Quantitative changes in the synaptic vesicle proteins synapsin I and p38 and the astrocyte-specific protein glial fibrillary acidic protein are associated with chemical-induced injury to the rat central nervous system. J Neurosci 7:931–942

    PubMed  Google Scholar 

  • Centers for Disease Control (1991) Preventing lead poisoning in young children. Centers for Disease Control, Atlanta

    Google Scholar 

  • Eisinger J (1978) Biochemistry and measurement of environmental lead intoxication. Q Rev Biophys 11:439–466

    PubMed  Google Scholar 

  • Eng LF (1985) Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol 8:203–214

    PubMed  Google Scholar 

  • Eng LF, DeArmond SJ (1982) Immunocytochemical studies of astrocytes in normal development and disease. Adv Cell Neurobiol 3:145–171

    Google Scholar 

  • Fedoroff S (1986) Prenatal ontogenesis of astrocytes. In: Fedoroff S, Vernadakis A (eds) Astrocytes, vol 1. Academic Press, New York, pp 35–74

    Google Scholar 

  • Gebhart AM, Goldstein GW (1988) Use of an in vitro system to study the effects of lead on astrocyte-endothelial cell interactions: a model for studying toxic injury to the blood-brain barrier. Toxicol Appl Pharmacol 94:191–206

    PubMed  Google Scholar 

  • Goldstein GW (1992) Neurologic concepts of lead poisoning in children. Pediatr Ann 21:384–388

    PubMed  Google Scholar 

  • Goldstein GW, Diamond I (1974) Metabolic basis of lead encephalopathy. Res Publ Assoc Res Nerv Ment Dis 53:293–304

    PubMed  Google Scholar 

  • Goodlett CR, Leo JT, O'Callaghan JP, Mahoney JC, West JR (1993) Transient cortical astrogliosis induced by alcohol exposure during the neonatal brain growth spurt in rats. Dev Brain Res 72:85–97

    Google Scholar 

  • Haglid KG, Wang S, Hamberger A, Lehmann A, Moller CJ (1991) Neuronal and glial marker proteins in the evaluation of the protective action of MK 801. J Neurochem 56:1957–1961

    PubMed  Google Scholar 

  • Harris KM, Teyler TJ (1984) Developmental onset of long-term potentiation in area CA1 of the rat hippocampus. J Physiol (Lond) 206:27–48

    Google Scholar 

  • Herrera DG, Cuello AC (1992) MK-801 affects the potassium-induced increase of glial fibrillary acidic protein immunoreactivity in the rat brain. Brain Res 598:286–293

    PubMed  Google Scholar 

  • Holtzman D, DeVries C, Nguyen H, Jameson N, Olson J, Carrithers M, Bensch K (1982) Development of resistance to lead encephalopathy during maturation in the rat pup. J Neuropathol Exp Neurol 41:652–663

    PubMed  Google Scholar 

  • Holtzman D, DeVries C, Nguyen H, Olson J, Bensch K (1984) Maturation of resistance to lead encephalopathy: cellular and subcellular mechanisms. Neurotoxicology 5:97–124

    Google Scholar 

  • Holtzman D, Olson JE, DeVries C, Bensch K (1987) Lead toxicity in primary cultured cerebral astrocytes and cerebellar granular neurons. Toxicol Appl Pharmacol 89:211–225

    PubMed  Google Scholar 

  • Honovar M, Lantos PL (1987) Ultrastructural changes in the frontal cortex and hippocampus in the ageing marmoset. Mech Ageing Dev 41:161–175

    PubMed  Google Scholar 

  • Janzer RC, Raff MC (1987) Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 325:253–257

    PubMed  Google Scholar 

  • Jugo S (1977) Metabolism of toxic heavy metals in growing organisms: a review. Environ Res 13:36–46

    PubMed  Google Scholar 

  • Julshamm K, Andersen KJ (1979) A study on the digestion of human muscle biopsies for trace metal analysis using an organic tissue solubilizer. Anal Biochem 98:315–318

    PubMed  Google Scholar 

  • Kiraly E, Jones DG (1982) Dendritic spine changes in rat hippocampal pyramidal cells after postnatal lead treatment: a Golgi study. Exp Neurol 77:236–239

    PubMed  Google Scholar 

  • Kraig RP, Dong L, Thisted R, Jaeger CB (1991) Spreading depression increases immunohistochemical staining of glial fibrillary acidic protein. J Neurosci 11:2187–2198

    PubMed  Google Scholar 

  • Laundry CF, Ivo GO, Brown IR (1990) Developmental expression of glial fibrillary acidic protein in the rat brain analysed by in situ hybridization. J Neurosci Res 25:194–203

    PubMed  Google Scholar 

  • Lewis SA, Balcarek JM, Krek V, Shelnasky M, Cowan N (1984) Sequence of a cDNA clone encoding mouse glial fibrillary acidic protein: structural conservation of intermediate filaments. Proc Natl Acad Sci USA 81:2743–2746

    PubMed  Google Scholar 

  • Lilienthal H, Winneke G (1991) Sensitive periods for behavioral toxicity of polychlorinated biphenyls: determination by crossfostering in rats. Fundam Appl Toxicol 17:368–375

    PubMed  Google Scholar 

  • Miller MW, Potempa G (1990) Numbers of neutrons and glia in mature rat somatosensory cortex: effects of prenatal exposure to ethanol. J Comp Neurol 293:92–102

    PubMed  Google Scholar 

  • Moore IE, Buontempo JM, Weller RO (1987) Response of fetal and neonatal rat brain to injury. Neuropathol Appl Neurobiol 13:219–228

    PubMed  Google Scholar 

  • Nathaniel EJH, Nathaniel DR (1981) The reactive astrocyte. In: Nathaniel EJH, Nathaniel DR (eds) Advances in cellular neurobiology, vol 2. Academic Press, New York, pp 249–301

    Google Scholar 

  • Needleman HL (1990a) The future challenge of lead toxicity. Environ Health Perspect 89:85–89

    PubMed  Google Scholar 

  • Needleman HL (1990b) What can be study of lead teach us about other toxicants. Eviron Health Perspect 86:183–189

    Google Scholar 

  • Norton WT, Aquino DA, Hozumi I, Chiu FC, Brosnan CETI (1992) Quantitative aspects of reactive gliosis: a review. Neurochem Res 17:877–885

    PubMed  Google Scholar 

  • O'Callaghan JP (1991) Assessment of neurotoxicity: use of glial fibrillary acidic protein as a biomarker. Biomed Environ Sci 4:197–206

    PubMed  Google Scholar 

  • O'Callaghan JP (1988) Neurotypic and gliotypic proteins as biochemical markers of neurotoxicity. Neurotoxicol Teratol 10:445–452

    PubMed  Google Scholar 

  • O'Callaghan JP, Miller DB (1989) Assessment of chemically-induced alterations in brain development using assays of neuron-and glia-localized proteins. Neurotoxicology 10:393–406

    PubMed  Google Scholar 

  • Pentschew A, Garro F (1966) Lead encephalo-myelopathy of the suckling rat and its implications on the porphyrinopathic nervous diseases. With special reference to the permeability disorders of the nervous system's capillaries. Acta Neuropathol (Berl) 6:266–278

    Google Scholar 

  • Perlmutter LS, Tweedle CD, Hatton GI (1984) Neuronal/glial plasticity in the supraoptic dendritic zone: dendritic bundling and double synapse formation at parturition. Neuroscience 13:769–779

    PubMed  Google Scholar 

  • Petit TL, Alfano DP, LeBoutillier JC (1983) Early lead exposure and the hippocampus: a review and recent advances. Neurotoxicology 4:79–94

    PubMed  Google Scholar 

  • Petito CK, Morgello S, Felix JC Lesser ML (1990) The two patterns of reactive astrocytosis in postischemic rat brain. J Cereb Blood Flow Metab 10:850–859

    PubMed  Google Scholar 

  • Rader JI, Celesk EM, Peeler JT, Mahaffey KR (1983) Retention of lead acetate in weanling and adult rats. Toxicol Appl Pharmacol 67:100–109

    PubMed  Google Scholar 

  • Rataboul P, Faucon Biguet N, Vernier P, de Vitry F, Boularand S, Privat A and Mallet J (1988) Identification of a human glial fibrillary acidic protein cDNA: a tool for the molecular analysis of reactive gliosis in the mammalian central nervous system. J Neurosci Res 20:165–175

    PubMed  Google Scholar 

  • Rosenbluth J (1988) Role of glial cells in the differentiation and function of myclinated axons. Int J Dev Neurosci 6:3–24

    PubMed  Google Scholar 

  • Rosene D, Van Hoesen GW (1987) The hippocampal formation of the primate brain. In: Jones EG, Peters A (eds) Cerebral cortex, vol 6. Plenum Press, New York, pp 345–455

    Google Scholar 

  • Schlessinger AR, Cowan WM, Gottlieb DI (1975) An autoradographic study of the time of origin and the pattern of granule cell migration in the dentate gyrus of the rat. J Comp Neurol 159:149–175

    PubMed  Google Scholar 

  • Selvin-Testa A, Lopez-Costa JJ, Nessi-de-Avinon AC, Pecci-Saavedra J (1991) Astroglial alterations in rat hippocampus during chronic lead exposure. Glia 4:384–392

    PubMed  Google Scholar 

  • Somogyi P, Takagi H (1982) A note on the use of picric acid-paraformaldehyde-glutaraldehyde fixative for correlated light and electron microscopic immunocytochemistry. Neuroscience 7:1779–1783

    PubMed  Google Scholar 

  • Stewart O, Torre ER, Phillps LL, Trimmer PA (1990) The process of reinnervation in the dentate gyrus of adult rats: time course of increase in mRNA for glial fibriallary acidic protein. J Neurosci 10:2373–2384

    PubMed  Google Scholar 

  • Sturrock RR (1980) A comparative quantitative and morphological study of ageing in the mouse neostriatum, induseum griseum and anterior commissure. Neuropathol Appl Neurobiol 6:51–68

    PubMed  Google Scholar 

  • Takamiaya Y, Kohsaka S, Toya, S, Otani M, Tsukada Y (1988) Immunohistochemical studies on the proliferation of reactive astrocytes and the expression of cytoskeletal proteins following brain injury in rats. Dev Brain Res 38:201–210

    Google Scholar 

  • Tiffany-Castiglioni E (1993) Cell culture models for lead toxicity in neuronal and glial cells. Neurotoxicology 14:513–536

    PubMed  Google Scholar 

  • Tiffany-Castiglioni E, Sierra EM, Wu JN, Rowles TK (1989) Lead toxicity in neuroglia. Neurotoxicology 10:417–443

    PubMed  Google Scholar 

  • Tiffany-Castiglioni E, Zmudzki J, Bratton GR (1986) Cellular targets of lead neurotoxicity: in vitro models. Toxicology 42:303–315

    PubMed  Google Scholar 

  • Walsh TJ, Emerich DF (1988) The hippocampus as a common target of neurotoxic agents. Toxicology 49:137–140

    PubMed  Google Scholar 

  • Walsh TJ, Tilson HA (1984) Neurobehavioral toxicology of the organoleads. Neurotoxicology 5:67–86

    Google Scholar 

  • Willes RF, Lok E, Truelove JF Sundaram A (1977) Retention and tissue distribution of 210Pb(NO3)2 administered orally to infant and adult monkeys. J Toxicol Environ Health 3:395–406

    PubMed  Google Scholar 

  • Winder C, Garten LL, Lewis PD (1983) The morphological effects of lead on the developing central nervous system. Neuropathol Appl Neurobiol 9:87–108

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stoltenburg-Didinger, G., Pünder, I., Peters, B. et al. Glial fibrillary acidic protein and RNA expression in adult rat hippocampus following low-level lead exposure during development. Histochem Cell Biol 105, 431–442 (1996). https://doi.org/10.1007/BF01457656

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01457656

Keywords

Navigation