---
_id: '2595'
abstract:
- lang: eng
  text: Presynaptic metabotropic glutamate receptors (mGluRs) of group III constitute
    possible targets for putative neuroprotective drugs acting against glutamate excitotoxic
    insults. Indeed, in glutamatergic cerebellar granule neurones in culture, high
    concentrations of L-2-amino-4-phosphonobutyrate (L-AP4, above 0.3 mM, thus activating
    mGluR7) inhibit NMDA-induced cell death. In contrast, in striatal cultures which
    are enriched in GABAergic neurones, we show that high concentrations of L-AP4
    increased neuronal death in control as well as in NMDA-stimulated cultures. Moreover,
    similar results were obtained with the GABA(B)R agonist, baclofen. Both the neuroprotective
    effects in cerebellar granule cells and the neurotoxic effects in striatal neurones
    were mediated via Gi-Go-coupled mGluRs, suggesting that these effects were probably
    mediated by mGluR7a or b and GABA(B)R expressed in these neurones. In striatal
    neurones, we found that L-AP4 and baclofen inhibited both basal and NMDA-stimulated
    GABA release. These inhibitions of GABA release may be responsible for the increase
    in basal and NMDA-stimulated neuronal death. Indeed, blockade of GABA(A) receptors
    with bicuculline increased neuronal death of control and NMDA-treated striatal
    cultures. Taken together, these results suggest that L-AP4 and baclofen, via mGluR7
    and GABA(B)R, reduced the neuroprotective effect of GABA present in striatal cultures
    acting via GABA(A) receptors. Although caution must be taken when extrapolating
    from in vitro to in vivo situations, the present experiments and the recent observations
    that mGluR7 and GABA(B)R are expressed in heterologous synapses, should be taken
    into consideration when evaluating the neuroprotective action of future mGluR7
    specific agonists or GABA(B)R specific antagonists.
acknowledgement: "We thank A. Turner-Madeuf for English revision, M. Passama and L.
  Charvet for the illustrations, Isabelle Brabet, Cécile Joly and Jaroslav Blahos
  for helpful technical assistance. This work was supported by the CNRS, Bayer \r\nFrance/Troponwerke
  (Germany), and CEE-Biomed BMH4-2 CT 960228."
article_processing_charge: No
article_type: original
author:
- first_name: Mireille
  full_name: Lafon Cazal, Mireille
  last_name: Lafon Cazal
- first_name: Gaëlle
  full_name: Viennois, Gaëlle
  last_name: Viennois
- first_name: Rainer
  full_name: Kühn, Rainer
  last_name: Kühn
- first_name: Barbara
  full_name: Malitschek, Barbara
  last_name: Malitschek
- first_name: Jean
  full_name: Pin, Jean
  last_name: Pin
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Joël
  full_name: Bockaërt, Joël
  last_name: Bockaërt
citation:
  ama: Lafon Cazal M, Viennois G, Kühn R, et al. mGluR7-like receptor and GABA(B)
    receptor activation enhance neurotoxic effects of N-methyl-D-aspartate in cultured
    mouse striatal GABAergic neurones. <i>Neuropharmacology</i>. 1999;38(10):1631-1640.
    doi:<a href="https://doi.org/10.1016/S0028-3908(99)00124-0">10.1016/S0028-3908(99)00124-0</a>
  apa: Lafon Cazal, M., Viennois, G., Kühn, R., Malitschek, B., Pin, J., Shigemoto,
    R., &#38; Bockaërt, J. (1999). mGluR7-like receptor and GABA(B) receptor activation
    enhance neurotoxic effects of N-methyl-D-aspartate in cultured mouse striatal
    GABAergic neurones. <i>Neuropharmacology</i>. Elsevier. <a href="https://doi.org/10.1016/S0028-3908(99)00124-0">https://doi.org/10.1016/S0028-3908(99)00124-0</a>
  chicago: Lafon Cazal, Mireille, Gaëlle Viennois, Rainer Kühn, Barbara Malitschek,
    Jean Pin, Ryuichi Shigemoto, and Joël Bockaërt. “MGluR7-like Receptor and GABA(B)
    Receptor Activation Enhance Neurotoxic Effects of N-Methyl-D-Aspartate in Cultured
    Mouse Striatal GABAergic Neurones.” <i>Neuropharmacology</i>. Elsevier, 1999.
    <a href="https://doi.org/10.1016/S0028-3908(99)00124-0">https://doi.org/10.1016/S0028-3908(99)00124-0</a>.
  ieee: M. Lafon Cazal <i>et al.</i>, “mGluR7-like receptor and GABA(B) receptor activation
    enhance neurotoxic effects of N-methyl-D-aspartate in cultured mouse striatal
    GABAergic neurones,” <i>Neuropharmacology</i>, vol. 38, no. 10. Elsevier, pp.
    1631–1640, 1999.
  ista: Lafon Cazal M, Viennois G, Kühn R, Malitschek B, Pin J, Shigemoto R, Bockaërt
    J. 1999. mGluR7-like receptor and GABA(B) receptor activation enhance neurotoxic
    effects of N-methyl-D-aspartate in cultured mouse striatal GABAergic neurones.
    Neuropharmacology. 38(10), 1631–1640.
  mla: Lafon Cazal, Mireille, et al. “MGluR7-like Receptor and GABA(B) Receptor Activation
    Enhance Neurotoxic Effects of N-Methyl-D-Aspartate in Cultured Mouse Striatal
    GABAergic Neurones.” <i>Neuropharmacology</i>, vol. 38, no. 10, Elsevier, 1999,
    pp. 1631–40, doi:<a href="https://doi.org/10.1016/S0028-3908(99)00124-0">10.1016/S0028-3908(99)00124-0</a>.
  short: M. Lafon Cazal, G. Viennois, R. Kühn, B. Malitschek, J. Pin, R. Shigemoto,
    J. Bockaërt, Neuropharmacology 38 (1999) 1631–1640.
date_created: 2018-12-11T11:58:34Z
date_published: 1999-10-01T00:00:00Z
date_updated: 2022-09-13T08:23:20Z
day: '01'
doi: 10.1016/S0028-3908(99)00124-0
extern: '1'
external_id:
  pmid:
  - '10530824 '
intvolume: '        38'
issue: '10'
language:
- iso: eng
month: '10'
oa_version: None
page: 1631 - 1640
pmid: 1
publication: Neuropharmacology
publication_identifier:
  issn:
  - 0028-3908
publication_status: published
publisher: Elsevier
publist_id: '4302'
quality_controlled: '1'
scopus_import: '1'
status: public
title: mGluR7-like receptor and GABA(B) receptor activation enhance neurotoxic effects
  of N-methyl-D-aspartate in cultured mouse striatal GABAergic neurones
type: journal_article
user_id: ea97e931-d5af-11eb-85d4-e6957dddbf17
volume: 38
year: '1999'
...
---
_id: '2597'
abstract:
- lang: eng
  text: Metabotropic glutamate receptors (mGlus) are known to modulate synaptic transmission
    in various pathways of the central nervous system, but the exact mechanisms by
    which this modulation occurs remain unclear. Here we utilise electrophysiological
    and immunocytochemical techniques on cultured autaptic hippocampal neurones to
    investigate the mechanism of action and distribution of mGlus. Agonists at all
    three groups of mGlus depressed glutamatergic transmission, whereas only agonists
    at group I mGlus depressed GABAergic transmission. Agonists at all mGlus failed
    to modulate Ca2+ and K+ channels in glutamatergic autapses whereas an agonist
    at group III mGlus did depress the frequency of miniature excitatory postsynaptic
    currents (mEPSCs). Agonists failed to modulate Ca2+ or K+ channels and miniature
    inhibitory postsynaptic currents (mIPSCs) in GABAergic autapses. Distribution
    studies using selective antibodies revealed punctate staining for group III mGlus
    that co-localised with the synaptic marker, synaptophysin. Staining for the remaining
    mGlus was more diffuse throughout the soma and processes with little co-localisation
    with synaptophysin. The distribution of the group III receptors is consistent
    with the direct 'downstream' modulation of mEPSCs, although the exact mechanism
    of action for the remaining receptors remains unclear.
acknowledgement: This work was supported by a Wellcome International Travel Fellowship
  to TJB and by the Public Service Grants DA02121, MH40165, NS33502 and NS33826 for
  CCL and RJM. We are grateful to Dr Graeme I. Bell for use of his microscope for
  the antibody studies.
article_processing_charge: No
article_type: original
author:
- first_name: Trevor
  full_name: Bushell, Trevor
  last_name: Bushell
- first_name: Chong
  full_name: Lee, Chong
  last_name: Lee
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Richard
  full_name: Miller, Richard
  last_name: Miller
citation:
  ama: Bushell T, Lee C, Shigemoto R, Miller R. Modulation of synaptic transmission
    and differential localisation of mGlus in cultured hippocampal autapses. <i>Neuropharmacology</i>.
    1999;38(10):1553-1567. doi:<a href="https://doi.org/10.1016/S0028-3908(99)00103-3">10.1016/S0028-3908(99)00103-3</a>
  apa: Bushell, T., Lee, C., Shigemoto, R., &#38; Miller, R. (1999). Modulation of
    synaptic transmission and differential localisation of mGlus in cultured hippocampal
    autapses. <i>Neuropharmacology</i>. Elsevier. <a href="https://doi.org/10.1016/S0028-3908(99)00103-3">https://doi.org/10.1016/S0028-3908(99)00103-3</a>
  chicago: Bushell, Trevor, Chong Lee, Ryuichi Shigemoto, and Richard Miller. “Modulation
    of Synaptic Transmission and Differential Localisation of MGlus in Cultured Hippocampal
    Autapses.” <i>Neuropharmacology</i>. Elsevier, 1999. <a href="https://doi.org/10.1016/S0028-3908(99)00103-3">https://doi.org/10.1016/S0028-3908(99)00103-3</a>.
  ieee: T. Bushell, C. Lee, R. Shigemoto, and R. Miller, “Modulation of synaptic transmission
    and differential localisation of mGlus in cultured hippocampal autapses,” <i>Neuropharmacology</i>,
    vol. 38, no. 10. Elsevier, pp. 1553–1567, 1999.
  ista: Bushell T, Lee C, Shigemoto R, Miller R. 1999. Modulation of synaptic transmission
    and differential localisation of mGlus in cultured hippocampal autapses. Neuropharmacology.
    38(10), 1553–1567.
  mla: Bushell, Trevor, et al. “Modulation of Synaptic Transmission and Differential
    Localisation of MGlus in Cultured Hippocampal Autapses.” <i>Neuropharmacology</i>,
    vol. 38, no. 10, Elsevier, 1999, pp. 1553–67, doi:<a href="https://doi.org/10.1016/S0028-3908(99)00103-3">10.1016/S0028-3908(99)00103-3</a>.
  short: T. Bushell, C. Lee, R. Shigemoto, R. Miller, Neuropharmacology 38 (1999)
    1553–1567.
date_created: 2018-12-11T11:58:35Z
date_published: 1999-10-01T00:00:00Z
date_updated: 2022-09-13T08:15:55Z
day: '01'
doi: 10.1016/S0028-3908(99)00103-3
extern: '1'
external_id:
  pmid:
  - '10530817'
intvolume: '        38'
issue: '10'
language:
- iso: eng
month: '10'
oa_version: None
page: 1553 - 1567
pmid: 1
publication: Neuropharmacology
publication_identifier:
  issn:
  - 0028-3908
publication_status: published
publisher: Elsevier
publist_id: '4301'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Modulation of synaptic transmission and differential localisation of mGlus
  in cultured hippocampal autapses
type: journal_article
user_id: ea97e931-d5af-11eb-85d4-e6957dddbf17
volume: 38
year: '1999'
...