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Neuroprotection induced by the adenosine A2A antagonist CSC in the 6-OHDA rat model of parkinsonism: effect on the activity of striatal output pathways

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Abstract

In Parkinson’s disease (PD), the striatal dopamine depletion and the following overactivation of the indirect pathway of the basal ganglia leads to very early disinhibition of the subthalamic nucleus (STN) that may contribute to the progression of PD by glutamatergic overstimulation of the dopaminergic neurons in the substantia nigra. Adenosine A2A antagonism has been demonstrated to attenuate the overactivity of the striatopallidal pathway. To investigate whether neuroprotection exerted by the A2A antagonist 8-(3-chlorostyryl)caffeine (CSC) correlates with a diminution of the striatopallidal pathway activity, we have examined the changes in the mRNA encoding for enkephalin, dynorphin, and adenosine A2A receptors by in situ hybridization induced by subacute systemic pretreatment with CSC in rats with striatal 6-hydroxydopamine(6-OHDA) administration. Animals received CSC for 7 days until 30 min before 6-OHDA intrastriatal administration. Vehicle-treated group received a solution of dimethyl sulfoxide. CSC pretreatment partially attenuated the decrease in nigral tyrosine hydroxylase immunoreactivity induced by 6-OHDA, whereas no modification of the increase in preproenkephalin mRNA expression in the dorsolateral striatum was observed. The neuroprotective effect of the adenosine A2A antagonist CSC in striatal 6-OHDA-lesioned rats does not result from a normalization of the increase in striatal PPE mRNA expression in the DL striatum, suggesting that other different mechanisms may be involved.

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Acknowledgements

This research was supported by grants from the Ministerio de Sanidad y Consumo (FIS 01/1499) and from the Ministerio de Ciencia y Tecnología (SAF2000–0212) of Spanish Government. J.B. and J.S. were supported by a grant from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). The research groups are a part of the Spanish network for the research of neurological diseases (CIEN, Centro de Investigación de Enfermedades Neurológicas).

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  1. Laboratori de Neurologia Experimental, Àrea de Neurociències, Fundació Clinic-Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036, Barcelona, Spain

    Jordi Bové, Eduardo Tolosa & Concepció Marin

  2. Departament de Neuroquímica, Institut d’Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPS, Barcelona, Spain

    Jordi Serrats, Guadalupe Mengod & Roser Cortés

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  1. Jordi Bové
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  2. Jordi Serrats
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  3. Guadalupe Mengod
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  4. Roser Cortés
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  5. Eduardo Tolosa
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  6. Concepció Marin
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Correspondence to Concepció Marin.

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Bové, J., Serrats, J., Mengod, G. et al. Neuroprotection induced by the adenosine A2A antagonist CSC in the 6-OHDA rat model of parkinsonism: effect on the activity of striatal output pathways. Exp Brain Res 165, 362–374 (2005). https://doi.org/10.1007/s00221-005-2302-1

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  • DOI: https://doi.org/10.1007/s00221-005-2302-1

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