Spinal cord mGlu1a receptors: Possible target for amyotrophic lateral sclerosis therapy

Alessandra Valerio, Marina Ferrario, Marta Paterlini, Paolo Liberini, Giuseppe Moretto, Nigel J. Cairns, Marina Pizzi, PierFranco Spano

Research output: Contribution to journalArticle

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of motor neurons, whose pathogenesis, probably multifactorial, is thought to involve AMPA/kainate receptor-mediated Ca2+ influx and excitotoxicity. We evaluated the possible involvement of Group I metabotropic glutamate (mGlu) receptors in the control of motor neuron viability. mGlu1a receptor distribution was analyzed in rat and human spinal cord by immunohistochemistry. In both species, the expression of mGlu1a receptor was developmentally regulated and showed a general trend to increase during foetal and postnatal maturation, reaching the maximum level of expression in the dorsal laminae I-II and in motor neurons in adult life. Exposure of spinal cord slices from adult rats to 300 μM kainate for 30 min induced motor neuron death, which was prevented by the Group I mGlu receptor agonist 3-hydroxyphenylglycine (3-HPG; 100 μM). Since motor neurons do not express mGlu5 receptors, mGlu1a receptor activation might be responsible for the observed neuroprotection. mGlu1a immunohistochemistry was conducted on spinal cord autoptic specimens from ALS and control subjects. Surviving motor neurons from ALS spinal cord still revealed the presence of mGlu1a at levels comparable to that from controls. We suggest that mGlu1a receptors may act as suitable targets for ALS experimental therapies.

Original languageEnglish
Pages (from-to)447-454
Number of pages8
JournalPharmacology, Biochemistry and Behavior
Volume73
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • Amyotrophic lateral sclerosis
  • Development
  • Human
  • Metabotropic glutamate receptor
  • Motor neurons
  • Rat
  • Spinal cord

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

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  • Cite this

    Valerio, A., Ferrario, M., Paterlini, M., Liberini, P., Moretto, G., Cairns, N. J., Pizzi, M., & Spano, P. (2002). Spinal cord mGlu1a receptors: Possible target for amyotrophic lateral sclerosis therapy. Pharmacology, Biochemistry and Behavior, 73(2), 447-454. https://doi.org/10.1016/S0091-3057(02)00835-3