Neuroprotection by metabotropic glutamate receptor agonists on kainate-induced degeneration of motor neurons in spinal cord slices from adult rat

M. Pizzi, M. Benarese, F. Boroni, F. Goffi, A. Valerio, P. F. Spano

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Research has provided evidence about the role of excitotoxicity in the pathophysiology of sporadic amyotrophic lateral sclerosis and suggests that AMPA/kainate receptor activation contributes greatly in mediating glutamate injury to motor neurons. The recent finding of variable expression of metabotropic glutamate (mGlu) receptor subtypes in adult rat spinal cord has prompted us to investigate their contribution to the excitotoxic process.We report here that stimulation of mGlu receptors efficiently prevents motor neuron degeneration induced by kainate. The application of kainate to lumbar spinal cord slices from adult rats induced a massive degeneration of motor neurons which became shrunken, dark and TUNEL-positive. On the contrary, no significant neurotoxicity was observed after NMDA application. A blockade of ionotropic non-NMDA receptors by CNQX, and mGlu receptor stimulation, efficiently counteracted kainate-mediated cell death. Among the various agonists for mGlu receptors, we tested 3-hydroxyphenylglycine (3HPG), which selectively stimulates group I mGlu receptors. In addition, we tested 2-(carboxycyclopropyl)glycine (L-CCG-I) and 4-carboxy-3-hydroxyphenylglycine (4C3HPG), two selective agonists for group II receptors, as well as L-amino-4-phosphonobutyrate (L-AP4), a preferential agonist for group III.The results suggest that all three groups of mGlu receptors are involved in inhibiting excitotoxic phenomena mediated by kainate on spinal cord motor neurons. This was despite being localized differently and, possibly, activating different neuroprotective pathways. Copyright (C) 2000.

Original languageEnglish
Pages (from-to)903-910
Number of pages8
JournalNeuropharmacology
Volume39
Issue number5
DOIs
Publication statusPublished - Apr 2000

Fingerprint

Excitatory Amino Acid Agonists
Metabotropic Glutamate Receptors
Kainic Acid
Motor Neurons
Spinal Cord
6-Cyano-7-nitroquinoxaline-2,3-dione
Kainic Acid Receptors
Nerve Degeneration
AMPA Receptors
In Situ Nick-End Labeling
N-Methylaspartate
Glutamic Acid
Cell Death
Neuroprotection
Wounds and Injuries
Research

Keywords

  • Apoptosis
  • Excitotoxicity
  • Kainate
  • Metabotropic glutamate receptors
  • Motor neuron
  • NMDA
  • Spinal cord

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Neuroprotection by metabotropic glutamate receptor agonists on kainate-induced degeneration of motor neurons in spinal cord slices from adult rat. / Pizzi, M.; Benarese, M.; Boroni, F.; Goffi, F.; Valerio, A.; Spano, P. F.

In: Neuropharmacology, Vol. 39, No. 5, 04.2000, p. 903-910.

Research output: Contribution to journalArticle

Pizzi, M. ; Benarese, M. ; Boroni, F. ; Goffi, F. ; Valerio, A. ; Spano, P. F. / Neuroprotection by metabotropic glutamate receptor agonists on kainate-induced degeneration of motor neurons in spinal cord slices from adult rat. In: Neuropharmacology. 2000 ; Vol. 39, No. 5. pp. 903-910.
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