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

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 dopa...

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Published in:Experimental brain research 2005-09, Vol.165 (3), p.362-374
Main Authors: BOVE, Jordi, SERRATS, Jordi, CORTES, Guadalupe Mengod Roser, TOLOSA, Eduardo, MARIN, Concepcio
Format: Article
Language:English
Subjects:
Adenosine
Adenosine A2 Receptor Antagonists
Animals
Biological and medical sciences
Caffeine - analogs & derivatives
Caffeine - pharmacology
Cell Count
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Dopamine
Dynorphins - biosynthesis
Enkephalins - biosynthesis
Fundamental and applied biological sciences. Psychology
Globus Pallidus - physiology
Immunohistochemistry
In Situ Hybridization
Male
Medical sciences
Microinjections
Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration
Neostriatum - physiology
Neural Pathways - physiology
Neurology
Neuroprotective Agents
Oxidopamine - administration & dosage
Parkinson Disease, Secondary - chemically induced
Parkinson Disease, Secondary - drug therapy
Parkinson's disease
Protein Precursors - biosynthesis
Rats
Rats, Sprague-Dawley
Receptor, Adenosine A2A - biosynthesis
RNA, Messenger - biosynthesis
Stereotyped Behavior - drug effects
Substantia Nigra - cytology
Sympatholytics - administration & dosage
Tyrosine 3-Monooxygenase - metabolism
Vertebrates: nervous system and sense organs
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Summary: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.
ISSN:0014-4819
1432-1106
DOI:10.1007/s00221-005-2302-1