The metabotropic glutamate receptor agonist 1S,3R-ACPD stimulates and modulates NMDA receptor mediated excitotoxicity in organotypic hippocampal slice cultures
Abstract
The potential toxic effects of the metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and its interactions with the N-methyl-D-aspartate (NMDA) receptor were studied in hippocampal brain slice cultures, using densitometric measurements of the cellular uptake of propidium iodide (PI) to quantify neuronal degeneration. Cultures exposed to ACPD, showed a concentration (2-5 mM) and time (1-4 days) dependent increase in PI uptake in CA1, CA3 and dentate subfields after 24 h and 48 h of exposure, with CA1 pyramidal cells being most sensitive. The neurodegeneration induced by 2 mM ACPD was completely abolished by addition of 10 microM of the NMDA receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), while 20 microM of the 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainic acid receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) had no effect. Co-exposing cultures to a subtoxic dose of 300 microM ACPD together with 10 microM NMDA, which at this dose is known to induce a fairly selective degeneration of CA1 pyramidal cells, significantly increased the PI uptake in both CA1 and CA3, compared to cultures exposed to 10 microM NMDA only. Adding the 300 microM ACPD as pretreatment for 30 min followed by a 30 min wash in normal medium before the ACPD/NMDA co-exposure, eliminated the potentiation of NMDA toxicity. The potentiation was also blocked by addition of 10 or 100 microM 2-methyl-6-(phenylethynyl)pyridine (MPEP) (mGluR5 antagonist) during the co-exposure, while a corresponding addition of 10 or 100 microM 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) (mGluR1 antagonist) had no effect. We conclude that, stimulation of metabotropic glutamate receptors with ACPD at concentrations of 2 mM or higher induces a distinct subfield-related and time and concentration dependent pattern of hippocampal degeneration, and that ACPD at subtoxic concentrations modulates NMDA-induced excitotoxicity through the mGluR5 receptor in a time dependent way.
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mGluR5 stimulation is known to enhance NMDA receptor responses.
“mGluR5 stimulation is known to enhance NMDA-R responses (Blaabjerg et al., 2001).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Blaabjerg et al., 2001
Cites
A simple method for organotypic cultures of nervous tissue
Stoppini, L., Buchs, P., & Muller, D. (1991) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(91)90128-m · Cited by 3,097 · see citing works
The metabotropic glutamate receptors: Structure and functions
Pin, J., & Duvoisin, R. M. (1995) · Neuropharmacology · doi:10.1016/0028-3908(94)00129-g · Cited by 2,267 · see citing works
Pharmacological agents acting at subtypes of metabotropic glutamate receptors
Schoepp, D. D., Jane, D. E., & Monn, J. A. (1999) · Neuropharmacology · doi:10.1016/s0028-3908(99)00092-1 · Cited by 1,061 · see citing works
Wenzel, A., Fritschy, J., Möhler, H., & Benke, D. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68020469.x · Cited by 442 · see citing works
Metabotropic glutamate receptors: a new target for the therapy of neurodegenerative disorders?
Nicoletti, F., Bruno, V., Copani, A., Casabona, G., & Knöpfel, T. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)20019-0 · Cited by 433 · see citing works
Markers for neuronal degeneration in organotypic slice cultures
Noraberg, J., Kristensen, B. W., & Zimmer, J. (1999) · Brain Research Protocols · doi:10.1016/s1385-299x(98)00050-6 · Cited by 307 · see citing works
Self-citationOrganotypic cultures of neural tissue
Gähwiler, B. H. (1988) · Trends in Neurosciences · doi:10.1016/0166-2236(88)90007-0 · Cited by 253 · see citing works
Cellular and connective organization of slice cultures of the rat hippocampus and fascia dentata
Zimmer, J., & Gähwiler, B. H. (1984) · The Journal of Comparative Neurology · doi:10.1002/cne.902280310 · Cited by 245 · see citing works
Self-citationSacaan, A. I., & Schoepp, D. D. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90862-2 · Cited by 193 · see citing works
O’Leary, D. M., Movsesyan, V. A., Vicini, S., & Faden, A. I. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703715 · Cited by 192 · see citing works
Activation of group I mG1uRs potentiates NMDA responses in rat hippocampal slices
Fitzjohna, S. M., Irving, A. J., Palmer, M. J., Harvey, J., Lodge, D., & Collingridge, G. L. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12301-6 · Cited by 181 · see citing works
Vornov, J. J., Tasker, R. C., & Coyle, J. T. (1991) · Experimental Neurology · doi:10.1016/0014-4886(91)90079-r · Cited by 172 · see citing works
Bruno, V., Copani, A., Knöpfel, T., Kühn, R., Casabona, G., Albani, P. D., Condorelli, D. F., & Nicoletti, F. (1995) · Neuropharmacology · doi:10.1016/0028-3908(95)00077-j · Cited by 170 · see citing works
Nicoletti, F., Bruno, V., Catania, M. V., Battaglia, G., Copani, A., Barbagallo, G. M. V., Ceña, V., Sánchez‐Prieto, J., Spano, P., & Pizzi, M. (1999) · Neuropharmacology · doi:10.1016/s0028-3908(99)00102-1 · Cited by 169 · see citing works
Neuroprotection by both NMDA and non-NMDA receptor antagonists in in vitro ischemia
Pringle, A. K., Iannotti, F., Wilde, G. J. C., Chad, J. E., Seeley, P. J., & Sundström, L. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00089-9 · Cited by 157 · see citing works
Moreno, A. R., Sistiaga, A., Lerma, J., & Sánchez‐Prieto, J. (1998) · Neuron · doi:10.1016/s0896-6273(00)80665-0 · Cited by 137 · see citing works
McDonald, J., Fix, A., Tizzano, J. P., & Dd, S. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-10-04445.1993 · Cited by 131 · see citing works
Linden, D. J., Smeyne, M., & Connor, J. A. (1994) · Journal of Neurophysiology · doi:10.1152/jn.1994.71.5.1992 · Cited by 127 · see citing works
Matus, A. I., Bernhardt, R. R., Bodmer, R., & Alaimo, D. (1986) · Neuroscience · doi:10.1016/0306-4522(86)90253-8 · Cited by 124 · see citing works
del Rı́o, J. A., Heimrich, B., Soriano, E., et al. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90298-3 · Cited by 112 · see citing works
Pellegrini-Giampietro, D. E., Cozzi, A., Peruginelli, F., Leonardi, P., Meli, E., Pellicciari, R., & Moroni, F. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00786.x · Cited by 109 · see citing works
Vornov, J. J., Tasker, R. C., & Coyle, J. T. (1994) · Stroke · doi:10.1161/01.str.25.2.457 · Cited by 104 · see citing works
Nakao, N. (1995) · Experimental Neurology · doi:10.1016/0014-4886(95)90002-0 · Cited by 99 · see citing works
Differential kinetics of propidium iodide uptake in apoptotic and necrotic thymocytes
Vitale, M., Zamai, L., Mazzotti, G., Cataldi, A., & Falcieri, E. (1993) · Histochemistry and Cell Biology · doi:10.1007/bf00269095 · Cited by 98 · see citing works
Herrero, I., Miras‐Portugal, M. T., & Sánchez‐Prieto, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.4.1951 · Cited by 93 · see citing works
Pozzo‐Miller, L. D., Mahanty, N. K., Connor, J. A., & Landis, D. M. D. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90544-4 · Cited by 91 · see citing works
Schoepp, D. D., Johnson, B. G., True, R. A., et al. (1991) · European Journal of Pharmacology Molecular Pharmacology · doi:10.1016/0922-4106(91)90010-f · Cited by 86 · see citing works
Juurlink, B. H. J., & Hertz, L. (1993) · Developmental Brain Research · doi:10.1016/0165-3806(93)90175-a · Cited by 84 · see citing works
Antagonists for group I mGluRs attenuate excitotoxic neuronal death in cortical cultures
Strasser, U., Lobner, D., Behrens, M. M., Canzoniero, L. M. T., & Choi, D. W. (1998) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1998.00291.x · Cited by 84 · see citing works
Potentiation of NMDA and AMPA responses by group I mGluR in spinal cord motoneurons
Ugolini, A., Corsi, M., & Bordi, F. (1997) · Neuropharmacology · doi:10.1016/s0028-3908(97)00103-2 · Cited by 80 · see citing works
Pellegrini-Giampietro, D. E., Torregrossa, S. A., & Moroni, F. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb15503.x · Cited by 77 · see citing works
A submersion method to induce hypoxic damage in organotypic hippocampal cultures
Frantseva, M. V., Carlen, P. L., & El‐Beheiry, H. (1999) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(99)00030-8 · Cited by 68 · see citing works
Pringle, A. K., Sundström, L., Wilde, G. J. C., Williams, L. R., & lannotti, F. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12745-2 · Cited by 66 · see citing works
Roles of Metabotropic Glutamate Receptors in Brain Plasticity and Pathology
Miller, S., Kesslak, J. P., Romano, C., & Cotman, C. W. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb17506.x · Cited by 65 · see citing works
Excitotoxic effects of non-NMDA receptor agonists in organotypic corticostriatal slice cultures
Kristensen, B. W., Noraberg, J., Jakobsen, B., et al. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01833-8 · Cited by 48 · see citing works
Self-citationTrimethyltin (TMT) neurotoxicity in organotypic rat hippocampal slice cultures
Noraberg, J., Gramsbergen, J. B., Fonnum, F., et al. (1998) · Brain Research · doi:10.1016/s0006-8993(97)01358-9 · Cited by 46 · see citing works
Chen, Q., Surmeier, D. J., & Reiner, A. J. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7135 · Cited by 41 · see citing works
Hsu, S. S.-F., Newell, D. W., Tucker, A., Malouf, A. T., & Winn, H. R. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90756-0 · Cited by 36 · see citing works
Neurotoxicity in organotypic hippocampal slices mediated by adenosine analogues and nitric oxide
Barth, A., Newell, D. W., Nguyen, L. B., Winn, H. R., Wender, R., Meno, J. R., & Janigro, D. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00348-x · Cited by 36 · see citing works
Sistiaga, A., Herrero, I., Conquet, F., & Sánchez‐Prieto, J. (1998) · Neuropharmacology · doi:10.1016/s0028-3908(98)00129-4 · Cited by 35 · see citing works
Best, N., Sundström, L., Mitchell, J., & Wheal, H. V. (1996) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1996.tb01289.x · Cited by 29 · see citing works
Miller, S., Bridges, R. J., Chamberlin, A. R., et al. (1994) · European Journal of Pharmacology Molecular Pharmacology · doi:10.1016/0922-4106(94)90091-4 · Cited by 26 · see citing works
Small, D. L., Monette, R., Chakravarthy, B., et al. (1996) · Neuropharmacology · doi:10.1016/s0028-3908(96)00028-7 · Cited by 24 · see citing works
Simantov, R., Liu, W., Broutman, G., et al. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.01828.x · Cited by 21 · see citing works
Wang, Y., Qin, Z.-H., Nakai, M., & Chase, T. N. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00837-8 · Cited by 19 · see citing works
Colwell, C. S., Altemus, K. L., & Levine, M. S. (1996) · Brain Research · doi:10.1016/0006-8993(96)00479-9 · Cited by 17 · see citing works
(+)‐MCPG induces PKCε translocation in cortical synaptosomes through a PLD‐coupled mGluR
Pastorino, L., Colciaghi, F., Gardoni, F., et al. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00023.x · Cited by 16 · see citing works
(1S,3R)-ACPD, a metabotropic glutamate receptor agonist, enhances damage after global ischaemia
Henrich‐Noack, P., & Reymann, K. G. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(98)00865-6 · Cited by 15 · see citing works
ACPD-mediated slow-onset potentiation is associated with cell death in the rat CA1 region in vivo
Manahan‐Vaughan, D. (1999) · Neuropharmacology · doi:10.1016/s0028-3908(98)00210-x · Cited by 13 · see citing works
Group I metabotropic glutamate receptor agonist causes neurodegeneration in rat hippocampus.
Ong, W. Y., & Balcar, V. J. (1997) · PubMed · Cited by 11 · see citing works
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The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease
Ferreira, S. T., & Klein, W. L. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.08.003 · Cited by 442 · see citing works
- Authors
- Blaabjerg, M., Kristensen, B. W., Bonde, C., & Zimmer, J.
- Affiliations
- University of Southern Denmark (DK)
- Corresponding author
- Blaabjerg, Morten
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 898
- Issue
- 1
- Pages
- 91-104
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1976599886
- Cited by
- 29
- References
- 50
- Citations by year
- 2015: 1 · 2014: 2
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Keywords
- metabotropic glutamate receptor agonist, 1S,3R-ACPD, NMDA receptor, excitotoxicity, hippocampal slice cultures, neurodegeneration, CA1 pyramidal neurons, MK-801, NBQX, MPEP, mGluR5, mGluR1, mGluR2, mGluR3, mGluR4, mGluR6, mGluR7, mGluR8, neuroprotection
- MeSH terms
- Animals, Cycloleucine, Coloring Agents, Hippocampus, Immunohistochemistry, Microtubule-Associated Proteins, Nerve Tissue Proteins, Neurotoxins, Propidium, Quinoxalines, Staining and Labeling, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Dizocilpine Maleate, Rats, Wistar, Receptors, Metabotropic Glutamate, Excitatory Amino Acid Agonists, Excitatory Amino Acid Antagonists, Rats, In Vitro Techniques
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