Group II metabotropic glutamate receptors regulate the vulnerability to hypoxic brain damage

Alessandro Poli, Alina Beraudi, Luigi Villani, Marianna Storto, Giuseppe Battaglia, Valeria Di Giorgi Gerevini, Irene Cappuccio, Andrea Caricasole, Mara D'Onofrio, Ferdinando Nicoletti

Research output: Contribution to journalArticle

Abstract

We examined the expression of metabotropic glutamate (mGlu) receptors in species of fish that differ for their vulnerability to anoxic brain damage. Although expression of mGlu1a and mGlu5 receptors was similar in the brain of all species examined, expression of mGlu2/3 receptors was substantially higher in the brain of anoxia-tolerant species (i.e., the carp Carassius carassius and the goldfish Carassius auratus) than in the brain of species that are highly vulnerable to anoxic damage, such as the trouts Salmo trutta and Oncorhynchus mykiss. This difference was confirmed by measuring the mGlu2/3 receptor-mediated inhibition of forskolin-stimulated cAMP formation in slices prepared from the telencephalon of C. auratus and S. trutta. We exposed the goldfish C. auratus to water deprived of oxygen for 4 hr for the induction of hypoxic brain damage. Although the goldfish survived this treatment, the occurrence of apoptotic cell death could be demonstrated by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining and by the assessment of caspase-3 activity in different brain region. The extent of cell death was highest in the medulla oblongata, followed by the optic tectum, cerebellum, and hypothalamus. No cell death was found in the telencephalon. This regional pattern of hypoxic damage was inversely related to the expression of mGlu2/3 receptors, which was lowest in the medulla oblongata and highest in the telencephalon. Treatment of the goldfish with the brain permeant mGlu2/3 receptor antagonist LY341495 (1 mg/kg, i.p.) amplified anoxic damage throughout the brain and enabled the induction of cell death by anoxia in the telencephalon. In contrast, treatment of the goldfish with the mGlu2/3 receptor agonist LY379268 (0.5 or 1 mg/kg, i.p.) was highly protective against anoxic brain damage. Finally, exposure to the antagonist LY341495 (0.5 μm) greatly amplified the release of glutamate induced by hypoxia in slices prepared from the medulla oblongata and the telencephalon of the goldfish. We conclude that expression of mGlu2/3 receptors provides a major defensive mechanism against brain damage in anoxia-tolerant species.

Original languageEnglish
Pages (from-to)6023-6029
Number of pages7
JournalJournal of Neuroscience
Volume23
Issue number14
Publication statusPublished - Jul 9 2003

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Brain Hypoxia
Goldfish
Metabotropic Glutamate Receptors
Telencephalon
Medulla Oblongata
LY 341495
Cell Death
Brain
Carps
LY 379268
Cell Hypoxia
Uridine Triphosphate
DNA Nucleotidylexotransferase
Superior Colliculi
Trout
Oncorhynchus mykiss
Colforsin
Caspase 3
Cerebellum
Hypothalamus

Keywords

  • Anoxia
  • Apoptosis
  • Glutamate release
  • Goldfish
  • mGlu receptors
  • Neuroprotection

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Group II metabotropic glutamate receptors regulate the vulnerability to hypoxic brain damage. / Poli, Alessandro; Beraudi, Alina; Villani, Luigi; Storto, Marianna; Battaglia, Giuseppe; Di Giorgi Gerevini, Valeria; Cappuccio, Irene; Caricasole, Andrea; D'Onofrio, Mara; Nicoletti, Ferdinando.

In: Journal of Neuroscience, Vol. 23, No. 14, 09.07.2003, p. 6023-6029.

Research output: Contribution to journalArticle

Poli, A, Beraudi, A, Villani, L, Storto, M, Battaglia, G, Di Giorgi Gerevini, V, Cappuccio, I, Caricasole, A, D'Onofrio, M & Nicoletti, F 2003, 'Group II metabotropic glutamate receptors regulate the vulnerability to hypoxic brain damage', Journal of Neuroscience, vol. 23, no. 14, pp. 6023-6029.
Poli, Alessandro ; Beraudi, Alina ; Villani, Luigi ; Storto, Marianna ; Battaglia, Giuseppe ; Di Giorgi Gerevini, Valeria ; Cappuccio, Irene ; Caricasole, Andrea ; D'Onofrio, Mara ; Nicoletti, Ferdinando. / Group II metabotropic glutamate receptors regulate the vulnerability to hypoxic brain damage. In: Journal of Neuroscience. 2003 ; Vol. 23, No. 14. pp. 6023-6029.
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