Group I metabotropic glutamate autoreceptors induce abnormal glutamate exocytosis in a mouse model of amyotrophic lateral sclerosis

Autor: Anna Pittaluga, Carlo Tacchetti, Aldamaria Puliti, Cesare Usai, Marco Milanese, Tiziana Bonifacino, Silvia Di Prisco, Giambattista Bonanno, Pia Irene Anna Rossi, Francesco Giribaldi
Přispěvatelé: Giribaldi, F, Milanese, M, Bonifacino, T, Rossi, Pia, Di Prisco, S, Pittaluga, A, Tacchetti, Carlo, Puliti, A, Usai, C, Bonanno, G.
Rok vydání: 2013
Předmět:
Male
Inositol Phosphates
Receptor
Metabotropic Glutamate 5
animal diseases
Glycine
Glutamic Acid
Mice
Transgenic
Pharmacology
Receptors
Metabotropic Glutamate
Exocytosis
Mice
Mice
Neurologic Mutants
Cellular and Molecular Neuroscience
Superoxide Dismutase-1
Neurotoxicity
Animals
Humans
Pre-synaptic mGlu1 receptors
Autoreceptors
Aspartic Acid
Metabotropic glutamate receptor 8
Lumbar Vertebrae
Superoxide Dismutase
Metabotropic glutamate receptor 5
Chemistry
Metabotropic glutamate receptor 4
Metabotropic glutamate receptor 7
Metabotropic glutamate receptor 6
nutritional and metabolic diseases
Resorcinols
Amyotrophic lateral sclerosis
nervous system diseases
Disease Models
Animal
Spinal Cord
Biochemistry
Metabotropic glutamate receptor
Metabotropic glutamate receptor 1
Calcium
Female
Pre-synaptic mGlu5 receptors
Glutamate release
Metabotropic glutamate receptor 2
Excitatory Amino Acid Antagonists
Synaptosomes
Zdroj: Neuropharmacology 66 (2013): 253–263. doi:10.1016/j.neuropharm.2012.05.018
info:cnr-pdr/source/autori:Giribaldi F; Milanese M; Bonifacino T; Anna Rossi PI; Di Prisco S; Pittaluga A; Tacchetti C; Puliti A; Usai C; Bonanno G/titolo:Group I metabotropic glutamate autoreceptors induce abnormal glutamate exocytosis in a mouse model of amyotrophic lateral sclerosis/doi:10.1016%2Fj.neuropharm.2012.05.018/rivista:Neuropharmacology/anno:2013/pagina_da:253/pagina_a:263/intervallo_pagine:253–263/volume:66
ISSN: 0028-3908
DOI: 10.1016/j.neuropharm.2012.05.018
Popis: Glutamate-mediated excitotoxicity plays a major role in ALS and reduced astrocytic glutamate transport was suggested as a cause. Based on previous work we have proposed that abnormal release may represent another source of excessive glutamate. In this line, here we studied the modulation of glutamate release in ALS by Group I metabotropic glutamate (mGlu) receptors, that comprise mGlu1 and mGlu5 members. Synaptosomes from the lumbar spinal cord of SOD1/G93A mice, a widely used murine model for human ALS, and controls were used in release, confocal or electron microscopy and Western blot experiments. Concentrations of the mGlu1/5 receptor agonist 3,5-DHPG >0.3 μM stimulated the release of [(3)H]d- aspartate, used to label the releasing pools of glutamate, both in control and SOD1/G93A mice. At variance, ≤0.3 μM 3,5-DHPG increased [(3)H]d-aspartate release in SOD1/G93A mice only. Experiments with selective antagonists indicated the involvement of both mGlu1 and mGlu5 receptors, mGlu5 being preferentially involved in the high potency effects of 3,5-DHPG. High 3,5-DHPG concentrations increased IP3 formation in both mouse strains, whereas low 3,5-DHPG did it in SOD1/G93A mice only. Release experiments confirmed that 3,5-DHPG elicited [(3)H]d-aspartate exocytosis involving intra-terminal Ca(2+) release through IP3-sensitive channels. Confocal microscopy indicated the co-existence of both receptors presynaptically in the same glutamatergic nerve terminal in SOD1/G93A mice. To conclude, activation of mGlu1/5 receptors produced abnormal glutamate release in SOD1/G93A mice, suggesting that these receptors are implicated in ALS and that selective antagonists may be predicted for new therapeutic approaches. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
Databáze: OpenAIRE
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