Blockade of Adenosine Receptors by Caffeine Provides
Neuroprotection in a Lentiviral Mouse Model of Machado-Joseph
Disease
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1
University of Coimbra, PhD Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, Portugal
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2
University of Coimbra, Center for Neuroscience and Cell Biology, Portugal
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3
University of Coimbra, Faculty of Pharmacy, Portugal
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4
University of Coimbra, Institute of Biochemistry, Faculty of Medicine, Portugal
Machado Joseph Disease (MJD) or spinocerebellar ataxia type 3, a devastating brain disease, is one of the nine dominantly-inherited polyglutamine neurodegenerative disorders presently known, and it is considered to result from a toxic gain of function of mutant ataxin-3, a polyubiquitin-binding protein. The mechanisms accounting for neuronal degeneration are still largely unknown and there is currently no treatment available. One candidate strategy to manage MJD neurodegeneration might be the antagonism of adenosine A2A receptors (A2ARs). In fact, A2AR blockade has been shown to afford robust neuroprotection in different neurodegenerative disorders based on the key role of A2ARs to control glutamatergic transmission, apoptotic neuronal death, astrocytic function and neuroinflammation. This prompts the hypothesis that the manipulation of A2AR function might also be beneficial in MJD.
A non-selective antagonism of the A2AR function promoted by the chronic consumption of caffeine (applied through the drinking water – 1g/L) was carried out in a lentiviral mouse model of MJD (Alves et al, 2008). Preliminary data suggest that caffeine led to an increase in the number of mutant ataxin-3 intranuclear inclusions in the striatum, a reduction in the loss of immunoreactivity for the dopaminergic marker DARPP-32, a decrease in the number of pycnotic nuclei and a reduction of the MJD-associated astrogliosis over time, when compared to the control group that only drank water.
Further studies are necessary to confirm if blockade of A2ARs is indeed able to control striatal pathology associated with MJD.
Conference:
11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009.
Presentation Type:
Poster Presentation
Topic:
Neurodegenerative Disorders
Citation:
Goncalves
N,
Simoes
AT,
Cunha
RA and
Pereira-de-Almeida
L
(2009). Blockade of Adenosine Receptors by Caffeine Provides
Neuroprotection in a Lentiviral Mouse Model of Machado-Joseph
Disease.
Front. Neurosci.
Conference Abstract:
11th Meeting of the Portuguese Society for Neuroscience.
doi: 10.3389/conf.neuro.01.2009.11.105
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Received:
10 Aug 2009;
Published Online:
10 Aug 2009.
*
Correspondence:
Nelio Goncalves, University of Coimbra, PhD Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, Coimbra, Portugal, neliomotag@gmail.com