QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 28, 2004, 24(4):828-835; doi:10.1523/JNEUROSCI.3831-03.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (33) Citing Articles via Google Scholar Google Scholar Articles by Battaglia, G. Articles by Bruno, V. Search for Related Content PubMed PubMed Citation Articles by Battaglia, G. Articles by Bruno, V.

 Previous Article  |  Next Article 

Neurobiology of Disease
Endogenous Activation of mGlu5 Metabotropic Glutamate Receptors Contributes to the Development of Nigro-Striatal Damage Induced by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in Mice

Giuseppe Battaglia,¹ Carla L. Busceti,¹ Gemma Molinaro,¹ Francesca Biagioni,¹ Marianna Storto,¹ Francesco Fornai,^1,2 Ferdinando Nicoletti,^1,3 and Valeria Bruno^1,3

¹Istituto Neurologico Mediterraneo Neuromed, 86077 Pozzilli, Italy, ²Department of Human Morphology and Applied Biology, University of Pisa, 56126 Pisa, Italy, and ³Department of Human Physiology and Pharmacology, University La Sapienza, 00185 Roma, Italy

We combined the use of knock-out mice and subtype-selective antagonists [2-methyl-6-(phenylethynyl)pyridine (MPEP) and (E)-2-methyl-6-(2-phenylethenyl)-pyridine (SIB1893)] to examine whether endogenous activation of mGlu5 metabotropic glutamate receptors contributes to the pathophysiology of nigro-striatal damage in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. High doses of MPTP (four injections of 20 mg/kg, i.p., every 2 hr) induced a high mortality rate and a nearly total degeneration of the nigro-striatal pathway in wild-type mice. mGlu5 knock-out mice were less sensitive to MPTP toxicity, as shown by a higher survival and a milder nigro-striatal damage. Protection against MPTP (80 mg/kg) toxicity was also observed after MPEP injections (four injections of 5 mg/kg, i.p., 30 min before each MPTP injection). MPEP treatment did not further increase neuroprotection against 80 mg/kg of MPTP in mGlu5 knock-out mice, indicating that the drug acted by inhibiting mGlu5 receptors. In wild-type mice, MPEP was also neuroprotective when challenged against lower doses of MPTP (either 30 mg/kg, single injection, or four of 10 mg/kg injections). The action of MPEP was mimicked by SIB1893 but not by the mGlu1 receptor antagonist 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester. MPEP did not change the kinetics of 1-methyl-4-phenylpyridinium ion formation in the striatum of mice injected with MPTP. We conclude that mGlu5 receptors act as amplifiers of MPTP toxicity and that mGlu5 receptor antagonists may limit the extent of nigro-striatal damage in experimental models of parkinsonism.

Key words: basal ganglia; dopamine; MPTP toxicity; mGlu 5 receptors; neuroprotection; experimental parkinsonism

---

Received Aug 16, 2003; revised November 5, 2003; accepted November 6, 2003.

This article has been cited by other articles:

				E. E. Benarroch Metabotropic glutamate receptors: Synaptic modulators and therapeutic targets for neurologic disease Neurology, March 18, 2008; 70(12): 964 - 968. [Full Text] [PDF]

				D. Marazziti, S. Mandillo, C. Di Pietro, E. Golini, R. Matteoni, and G. P. Tocchini-Valentini GPR37 associates with the dopamine transporter to modulate dopamine uptake and behavioral responses to dopaminergic drugs PNAS, June 5, 2007; 104(23): 9846 - 9851. [Abstract] [Full Text] [PDF]

				G. Battaglia, C. L. Busceti, G. Molinaro, F. Biagioni, A. Traficante, F. Nicoletti, and V. Bruno Pharmacological activation of mGlu4 metabotropic glutamate receptors reduces nigrostriatal degeneration in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J. Neurosci., July 5, 2006; 26(27): 7222 - 7229. [Abstract] [Full Text] [PDF]

				A. Kachroo, L. R. Orlando, D. K. Grandy, J.-F. Chen, A. B. Young, and M. A. Schwarzschild Interactions between Metabotropic Glutamate 5 and Adenosine A2A Receptors in Normal and Parkinsonian Mice J. Neurosci., November 9, 2005; 25(45): 10414 - 10419. [Abstract] [Full Text] [PDF]

				P. H. Anborgh, C. Godin, M. Pampillo, G. K. Dhami, L. B. Dale, S. P. Cregan, R. Truant, and S. S. G. Ferguson Inhibition of Metabotropic Glutamate Receptor Signaling by the Huntingtin-binding Protein Optineurin J. Biol. Chem., October 14, 2005; 280(41): 34840 - 34848. [Abstract] [Full Text] [PDF]

				F. Fornai, O. M. Schluter, P. Lenzi, M. Gesi, R. Ruffoli, M. Ferrucci, G. Lazzeri, C. L. Busceti, F. Pontarelli, G. Battaglia, et al. Parkinson-like syndrome induced by continuous MPTP infusion: Convergent roles of the ubiquitin-proteasome system and {alpha}-synuclein PNAS, March 1, 2005; 102(9): 3413 - 3418. [Abstract] [Full Text] [PDF]

				D. Marazziti, E. Golini, S. Mandillo, A. Magrelli, W. Witke, R. Matteoni, and G. P. Tocchini-Valentini Altered dopamine signaling and MPTP resistance in mice lacking the Parkinson's disease-associated GPR37/parkin-associated endothelin-like receptor PNAS, July 6, 2004; 101(27): 10189 - 10194. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help