Abstract
Long term exposure to low doses of mercury or lead can induce neurasthenic symptoms with slight cognitive deficits, lability, fatigue, decreased stress tolerance, and decreased simultaneous capacity. After exposure to higher concentrations permanent neuropsychological deficits can be seen. The present paper gives a new idea of possible molecular mechanisms underlying the symptoms. Impairments of astrocyte function are probably important, especially due to their capacity to regulate the ionic and amino acid concentration in the extracellular micromilieu, brain energy metabolism, and cell volume. Recent results have shown that these functions are under monoaminergic control. Aspects of therapy are outlined.
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- Barres B. A., Chun L. L., Corey D. P. Calcium current in cortical astrocytes: induction by cAMP and neurotransmitters and permissive effect of serum factors. J Neurosci. 1989 Sep;9(9):3169–3175. doi: 10.1523/JNEUROSCI.09-09-03169.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bellinger D., Leviton A., Waternaux C., Needleman H., Rabinowitz M. Low-level lead exposure, social class, and infant development. Neurotoxicol Teratol. 1988 Nov-Dec;10(6):497–503. doi: 10.1016/0892-0362(88)90084-0. [DOI] [PubMed] [Google Scholar]
- Bergomi M., Borella P., Fantuzzi G., Vivoli G., Sturloni N., Cavazzuti G., Tampieri A., Tartoni P. L. Relationship between lead exposure indicators and neuropsychological performance in children. Dev Med Child Neurol. 1989 Apr;31(2):181–190. doi: 10.1111/j.1469-8749.1989.tb03977.x. [DOI] [PubMed] [Google Scholar]
- Bevan S., Chiu S. Y., Gray P. T., Ritchie J. M. The presence of voltage-gated sodium, potassium and chloride channels in rat cultured astrocytes. Proc R Soc Lond B Biol Sci. 1985 Sep 23;225(1240):299–313. doi: 10.1098/rspb.1985.0063. [DOI] [PubMed] [Google Scholar]
- Brookes N. Specificity and reversibility of the inhibition by HgCl2 of glutamate transport in astrocyte cultures. J Neurochem. 1988 Apr;50(4):1117–1122. doi: 10.1111/j.1471-4159.1988.tb10581.x. [DOI] [PubMed] [Google Scholar]
- Cambray-Deakin M., Pearce B., Morrow C., Murphy S. Effects of extracellular potassium on glycogen stores of astrocytes in vitro. J Neurochem. 1988 Dec;51(6):1846–1851. doi: 10.1111/j.1471-4159.1988.tb01167.x. [DOI] [PubMed] [Google Scholar]
- Cambray-Deakin M., Pearce B., Morrow C., Murphy S. Effects of neurotransmitters on astrocyte glycogen stores in vitro. J Neurochem. 1988 Dec;51(6):1852–1857. doi: 10.1111/j.1471-4159.1988.tb01168.x. [DOI] [PubMed] [Google Scholar]
- Chneiweiss H., Glowinski J., Prémont J. Vasoactive intestinal polypeptide receptors linked to an adenylate cyclase, and their relationship with biogenic amine- and somatostatin-sensitive adenylate cyclases on central neuronal and glial cells in primary cultures. J Neurochem. 1985 Mar;44(3):779–786. doi: 10.1111/j.1471-4159.1985.tb12883.x. [DOI] [PubMed] [Google Scholar]
- Choi B. H., Lapham L. W., Amin-Zaki L., Saleem T. Abnormal neuronal migration, deranged cerebral cortical organization, and diffuse white matter astrocytosis of human fetal brain: a major effect of methylmercury poisoning in utero. J Neuropathol Exp Neurol. 1978 Nov-Dec;37(6):719–733. doi: 10.1097/00005072-197811000-00001. [DOI] [PubMed] [Google Scholar]
- Cornell-Bell A. H., Finkbeiner S. M., Cooper M. S., Smith S. J. Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science. 1990 Jan 26;247(4941):470–473. doi: 10.1126/science.1967852. [DOI] [PubMed] [Google Scholar]
- Cummins C. J., Glover R. A., Sellinger O. Z. Neuronal cues regulate uptake in cultured astrocytes. Brain Res. 1979 Jul 6;170(1):190–193. doi: 10.1016/0006-8993(79)90953-3. [DOI] [PubMed] [Google Scholar]
- Dietrich K. N., Krafft K. M., Bornschein R. L., Hammond P. B., Berger O., Succop P. A., Bier M. Low-level fetal lead exposure effect on neurobehavioral development in early infancy. Pediatrics. 1987 Nov;80(5):721–730. [PubMed] [Google Scholar]
- Engle M. J., Volpe J. J. Glutamine synthetase activity of developing astrocytes is inhibited in vitro by very low concentrations of lead. Brain Res Dev Brain Res. 1990 Sep 1;55(2):283–287. doi: 10.1016/0165-3806(90)90210-p. [DOI] [PubMed] [Google Scholar]
- Foote S. L., Bloom F. E., Aston-Jones G. Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol Rev. 1983 Jul;63(3):844–914. doi: 10.1152/physrev.1983.63.3.844. [DOI] [PubMed] [Google Scholar]
- Greenamyre J. T. The role of glutamate in neurotransmission and in neurologic disease. Arch Neurol. 1986 Oct;43(10):1058–1063. doi: 10.1001/archneur.1986.00520100062016. [DOI] [PubMed] [Google Scholar]
- Hansson E. Astroglia from defined brain regions as studied with primary cultures. Prog Neurobiol. 1988;30(5):369–397. doi: 10.1016/0301-0082(88)90008-1. [DOI] [PubMed] [Google Scholar]
- Hansson E., Eriksson P., Nilsson M. Amino acid and monoamine transport in primary astroglial cultures from defined brain regions. Neurochem Res. 1985 Oct;10(10):1335–1341. doi: 10.1007/BF00964976. [DOI] [PubMed] [Google Scholar]
- Hansson E. Primary cultures from defined brain areas; effects of seeding time on the development of beta-adrenergic- and dopamine-stimulated cAMP-activity during cultivation. Brain Res. 1985 Aug;353(2):187–192. doi: 10.1016/0165-3806(85)90207-x. [DOI] [PubMed] [Google Scholar]
- Hansson E., Rönnbäck L. Interaction between catecholamines and vasoactive intestinal peptide in cultured astrocytes. Neuropharmacology. 1988 Mar;27(3):295–300. doi: 10.1016/0028-3908(88)90047-0. [DOI] [PubMed] [Google Scholar]
- Hansson E., Rönnbäck L. Receptor regulation of the glutamate, GABA and taurine high-affinity uptake into astrocytes in primary culture. Brain Res. 1991 May 10;548(1-2):215–221. doi: 10.1016/0006-8993(91)91124-j. [DOI] [PubMed] [Google Scholar]
- Hansson E., Rönnbäck L. Regulation of glutamate and GABA transport by adrenoceptors in primary astroglial cell cultures. Life Sci. 1989;44(1):27–34. doi: 10.1016/0024-3205(89)90214-2. [DOI] [PubMed] [Google Scholar]
- Hansson E., Simonsson P., Alling C. 5-Hydroxytryptamine stimulates the formation of inositol phosphate in astrocytes from different regions of the brain. Neuropharmacology. 1987 Sep;26(9):1377–1382. doi: 10.1016/0028-3908(87)90102-x. [DOI] [PubMed] [Google Scholar]
- Hansson E., Simonsson P., Alling C. Interactions between cyclic AMP and inositol phosphate transduction systems in astrocytes in primary culture. Neuropharmacology. 1990 Jun;29(6):591–598. doi: 10.1016/0028-3908(90)90072-y. [DOI] [PubMed] [Google Scholar]
- Holtzman D., DeVries C., Nguyen H., Olson J., Bensch K. Maturation of resistance to lead encephalopathy: cellular and subcellular mechanisms. Neurotoxicology. 1984 Fall;5(3):97–124. [PubMed] [Google Scholar]
- Hsu C. C., Hsu C. S. Effect of isoproterenol on the uptake of [14C]glucose into glial cells. Neurosci Res. 1990 Sep;9(1):54–58. doi: 10.1016/0168-0102(90)90045-g. [DOI] [PubMed] [Google Scholar]
- Ibrahim M. Z. Glycogen and its related enzymes of metabolism in the central nervous system. Adv Anat Embryol Cell Biol. 1975;52(1):3–89. doi: 10.1007/978-3-642-86875-7. [DOI] [PubMed] [Google Scholar]
- Janzer R. C., Raff M. C. Astrocytes induce blood-brain barrier properties in endothelial cells. Nature. 1987 Jan 15;325(6101):253–257. doi: 10.1038/325253a0. [DOI] [PubMed] [Google Scholar]
- Johnson R. D., Iuvone P. M., Minneman K. P. Regulation of alpha-1 adrenergic receptor density and functional responsiveness in rat brain. J Pharmacol Exp Ther. 1987 Sep;242(3):842–849. [PubMed] [Google Scholar]
- Kettenmann H., Orkand R. K., Schachner M. Coupling among identified cells in mammalian nervous system cultures. J Neurosci. 1983 Mar;3(3):506–516. doi: 10.1523/JNEUROSCI.03-03-00506.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kettenmann H., Ransom B. R. Electrical coupling between astrocytes and between oligodendrocytes studied in mammalian cell cultures. Glia. 1988;1(1):64–73. doi: 10.1002/glia.440010108. [DOI] [PubMed] [Google Scholar]
- Kimelberg H. K. Primary astrocyte cultures--a key to astrocyte function. Cell Mol Neurobiol. 1983 Mar;3(1):1–16. doi: 10.1007/BF00734994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lerea L. S., McCarthy K. D. Astroglial cells in vitro are heterogeneous with respect to expression of the alpha 1-adrenergic receptor. Glia. 1989;2(3):135–147. doi: 10.1002/glia.440020302. [DOI] [PubMed] [Google Scholar]
- MacVicar B. A. Voltage-dependent calcium channels in glial cells. Science. 1984 Dec 14;226(4680):1345–1347. doi: 10.1126/science.6095454. [DOI] [PubMed] [Google Scholar]
- Magistretti P. J., Schorderet M. VIP and noradrenaline act synergistically to increase cyclic AMP in cerebral cortex. Nature. 1984 Mar 15;308(5956):280–282. doi: 10.1038/308280a0. [DOI] [PubMed] [Google Scholar]
- McCarthy K. D. An autoradiographic analysis of beta adrenergic receptors on immunocytochemically defined astroglia. J Pharmacol Exp Ther. 1983 Jul;226(1):282–290. [PubMed] [Google Scholar]
- McCarthy K. D., de Vellis J. Alpah-adrenergic receptor modulation of beta-adrenergic, adenosine and prostaglandin E1 increased adenosine 3':5'-cyclic monophosphate levels in primary cultures of glia. J Cyclic Nucleotide Res. 1978 Feb;4(1):15–26. [PubMed] [Google Scholar]
- Moore R. Y., Bloom F. E. Central catecholamine neuron systems: anatomy and physiology of the norepinephrine and epinephrine systems. Annu Rev Neurosci. 1979;2:113–168. doi: 10.1146/annurev.ne.02.030179.000553. [DOI] [PubMed] [Google Scholar]
- Morrison J. H., Molliver M. E., Grzanna R., Coyle J. T. The intra-cortical trajectory of the coeruleo-cortical projection in the rat: a tangentially organized cortical afferent. Neuroscience. 1981;6(2):139–158. doi: 10.1016/0306-4522(81)90051-8. [DOI] [PubMed] [Google Scholar]
- Murphy S., Pearce B. Functional receptors for neurotransmitters on astroglial cells. Neuroscience. 1987 Aug;22(2):381–394. doi: 10.1016/0306-4522(87)90342-3. [DOI] [PubMed] [Google Scholar]
- Needleman H. L., Schell A., Bellinger D., Leviton A., Allred E. N. The long-term effects of exposure to low doses of lead in childhood. An 11-year follow-up report. N Engl J Med. 1990 Jan 11;322(2):83–88. doi: 10.1056/NEJM199001113220203. [DOI] [PubMed] [Google Scholar]
- Nilsson M., Hansson E., Rönnbäck L. Heterogeneity among astroglial cells with respect to 5HT-evoked cytosolic Ca2+ responses. A microspectrofluorimetric study on single cells in primary culture. Life Sci. 1991;49(18):1339–1350. doi: 10.1016/0024-3205(91)90198-k. [DOI] [PubMed] [Google Scholar]
- Oyake Y., Tanaka M., Kubo H., Chichibu M. [Neuropathological studies on organic mercury poisoning with special reference to the staining and distribution of mercury granules]. Shinkei Kenkyu No Shimpo. 1966 Dec;10(4):744–750. [PubMed] [Google Scholar]
- Parnavelas J. G., Papadopoulos G. C. The monoaminergic innervation of the cerebral cortex is not diffuse and nonspecific. Trends Neurosci. 1989 Sep;12(9):315–319. doi: 10.1016/0166-2236(89)90037-4. [DOI] [PubMed] [Google Scholar]
- Pearce B., Cambray-Deakin M., Morrow C., Grimble J., Murphy S. Activation of muscarinic and of alpha 1-adrenergic receptors on astrocytes results in the accumulation of inositol phosphates. J Neurochem. 1985 Nov;45(5):1534–1540. doi: 10.1111/j.1471-4159.1985.tb07224.x. [DOI] [PubMed] [Google Scholar]
- Petit T. L. Developmental effects of lead: its mechanism in intellectual functioning and neural plasticity. Neurotoxicology. 1986 Summer;7(2):483–495. [PubMed] [Google Scholar]
- Quandt F. N., MacVicar B. A. Calcium activated potassium channels in cultured astrocytes. Neuroscience. 1986 Sep;19(1):29–41. doi: 10.1016/0306-4522(86)90003-5. [DOI] [PubMed] [Google Scholar]
- Ransom B. R., Kettenmann H. Electrical coupling, without dye coupling, between mammalian astrocytes and oligodendrocytes in cell culture. Glia. 1990;3(4):258–266. doi: 10.1002/glia.440030405. [DOI] [PubMed] [Google Scholar]
- Rosenberg P. A., Dichter M. A. A small subset of cortical astrocytes in culture accumulates glycogen. Int J Dev Neurosci. 1987;5(3):227–235. doi: 10.1016/0736-5748(87)90033-5. [DOI] [PubMed] [Google Scholar]
- Salm A. K., McCarthy K. D. Expression of beta-adrenergic receptors by astrocytes isolated from adult rat cortex. Glia. 1989;2(5):346–352. doi: 10.1002/glia.440020507. [DOI] [PubMed] [Google Scholar]
- Schwartz J. P. Stimulation of nerve growth factor mRNA content in C6 glioma cells by a beta-adrenergic receptor and by cyclic AMP. Glia. 1988;1(4):282–285. doi: 10.1002/glia.440010407. [DOI] [PubMed] [Google Scholar]
- Sierra E. M., Tiffany-Castiglioni E. Reduction of glutamine synthetase activity in astroglia exposed in culture to low levels of inorganic lead. Toxicology. 1991 Jan;65(3):295–304. doi: 10.1016/0300-483x(91)90088-i. [DOI] [PubMed] [Google Scholar]
- Staub F., Baethmann A., Peters J., Weigt H., Kempski O. Effects of lactacidosis on glial cell volume and viability. J Cereb Blood Flow Metab. 1990 Nov;10(6):866–876. doi: 10.1038/jcbfm.1990.143. [DOI] [PubMed] [Google Scholar]
- Stone E. A., Ariano M. A. Are glial cells targets of the central noradrenergic system? A review of the evidence. Brain Res Brain Res Rev. 1989 Oct-Dec;14(4):297–309. doi: 10.1016/0165-0173(89)90015-5. [DOI] [PubMed] [Google Scholar]
- Subbarao K. V., Hertz L. Effect of adrenergic agonists on glycogenolysis in primary cultures of astrocytes. Brain Res. 1990 Dec 17;536(1-2):220–226. doi: 10.1016/0006-8993(90)90028-a. [DOI] [PubMed] [Google Scholar]
- Subbarao K. V., Hertz L. Noradrenaline induced stimulation of oxidative metabolism in astrocytes but not in neurons in primary cultures. Brain Res. 1990 Sep 17;527(2):346–349. doi: 10.1016/0006-8993(90)91157-c. [DOI] [PubMed] [Google Scholar]
- Sun D., Wekerle H. Ia-restricted encephalitogenic T lymphocytes mediating EAE lyse autoantigen-presenting astrocytes. Nature. 1986 Mar 6;320(6057):70–72. doi: 10.1038/320070a0. [DOI] [PubMed] [Google Scholar]
- Tiffany-Castiglioni E., Sierra E. M., Wu J. N., Rowles T. K. Lead toxicity in neuroglia. Neurotoxicology. 1989 Fall;10(3):417–443. [PubMed] [Google Scholar]
- Tiffany-Castiglioni E., Zmudzki J., Bratton G. R. Cellular targets of lead neurotoxicity: in vitro models. Toxicology. 1986 Dec 15;42(2-3):303–315. doi: 10.1016/0300-483x(86)90018-1. [DOI] [PubMed] [Google Scholar]
- Usowicz M. M., Gallo V., Cull-Candy S. G. Multiple conductance channels in type-2 cerebellar astrocytes activated by excitatory amino acids. Nature. 1989 Jun 1;339(6223):380–383. doi: 10.1038/339380a0. [DOI] [PubMed] [Google Scholar]
- Van Calker D., Müller M., Hamprecht B. Adrenergic alpha- and beta-receptors expressed by the same cell type in primary culture of perinatal mouse brain. J Neurochem. 1978 Apr;30(4):713–718. doi: 10.1111/j.1471-4159.1978.tb10776.x. [DOI] [PubMed] [Google Scholar]
- Walz W., Hertz L. Functional interactions between neurons and astrocytes. II. Potassium homeostasis at the cellular level. Prog Neurobiol. 1983;20(1-2):133–183. doi: 10.1016/0301-0082(83)90013-8. [DOI] [PubMed] [Google Scholar]
- Walz W., Hinks E. C. Carrier-mediated KCl accumulation accompanied by water movements is involved in the control of physiological K+ levels by astrocytes. Brain Res. 1985 Sep 16;343(1):44–51. doi: 10.1016/0006-8993(85)91156-4. [DOI] [PubMed] [Google Scholar]
- Wilkin G. P., Marriott D. R., Cholewinski A. J. Astrocyte heterogeneity. Trends Neurosci. 1990 Feb;13(2):43–46. doi: 10.1016/0166-2236(90)90065-i. [DOI] [PubMed] [Google Scholar]
- Wolfe B. B., Harden T. K., Sporn J. R., Molinoff P. B. Presynaptic modulation of beta adrenergic receptors in rat cerebral cortex after treatment with antidepressants. J Pharmacol Exp Ther. 1978 Nov;207(2):446–457. [PubMed] [Google Scholar]

