Neuroprotection through inactivation of neuronal forebrain A2A receptors in a mouse model of Parkinson's disease

Abstract

Event Abstract Back to Event Neuroprotection through inactivation of neuronal forebrain A2A receptors in a mouse model of Parkinson's disease Micaela Morelli1*, Schintu N1, Frau L. A1 and A. R. Carta1 1 University of Cagliari, Department of Toxicology, Italy Antagonism of A2A adenosine receptors (A2AR) displays neuroprotective effects in animal models of Parkinson’s disease (PD). In order to investigate whether neuroprotection by A2AR blockade is achieved through receptor located on neurons or on glial cells, we investigated neuroprotection in the subchronic MPTP mouse model of PD. MPTP (20 mg/kg) or vehicle were administered daily for 4 days in conditional knockout mice lacking A2AR postnatally on forebrain neurons (fbnA2AKO mice) or on astrocytes (astroA2AKO mice). Neuronal damage was evaluated by tyrosine hydroxylase immunoreactivity, whereas the inflammatory response in the SNc and in the striatum (Str) was studied through analysis of GFAP and CD11b immunoreactivity, as markers of astroglial and microglial cells respectively. In fbnA2A wild type (WT) and astroA2AWT mice, MPTP subchronic treatment induced loss of 30% of dopamine neurons in the SNc, while GFAP and Cd11b immunoreactivity was significantly enhanced in both areas. In fbnA2AKO mice, but not in astroA2AKO mice, MPTP-induced dopamine neurons degeneration was prevented. In fbnA2AKO mice, MPTP-induced increase in GFAP immunoreactivity was prevented in the SNc and partially counteracted in the Str, while CD11b activation was prevented in both SNc and Str. In contrast, in astroA2AKO mice, MPTP-induced GFAP and CD11b immunoreactivity was similar to WT littermates, in SNc and Str. Selective deletion of A2AR in forebrain neurons but not in astroglial cells protected dopamine neurons from MPTP toxicity and prevented MPTP-induced glial response. Data endorse a primary role of neuronal rather than glial A2A receptors in neuroprotection in a subchronic MPTP model of PD. Keywords: Adenosine, Dopamine, Parkinson Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Oral Presentation Citation: Morelli M, N S, A FL and Carta AR (2009). Neuroprotection through inactivation of neuronal forebrain A2A receptors in a mouse model of Parkinson's disease. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.081 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 Nov 2009; Published Online: 20 Nov 2009. * Correspondence: Micaela Morelli, University of Cagliari, Department of Toxicology, Cagliari, Italy, morelli@unica.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Micaela Morelli Schintu N Frau L A A. R Carta Google Micaela Morelli Schintu N Frau L A A. R Carta Google Scholar Micaela Morelli Schintu N Frau L A A. R Carta PubMed Micaela Morelli Schintu N Frau L A A. R Carta Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.