title: Neuroprotection induced by the adenosine A2A antagonist CSC in the 6-OHDA rat model of parkinsonism: effect on the activity of striatal output pathways.
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.
authors.affiliation: Laboratori de Neurologia Experimental, Area de Neurociències, Fundació Clinic-Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036 Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bové
authors.forename: Jordi
authors.initials: J
authors.lastname: Serrats
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Mengod
authors.forename: Roser
authors.initials: R
authors.lastname: Cortés
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.forename: Concepció
authors.initials: C
authors.lastname: Marin
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002452:Cell Count; D004399:Dynorphins / Q000096:biosynthesis; D004745:Enkephalins / Q000096:biosynthesis; D005917:Globus Pallidus / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008845:Microinjections; D017072:Neostriatum / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D018696:Neuroprotective Agents; D016627:Oxidopamine / Q000008:administration & dosage; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000096:biosynthesis; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000166:cytology; D013565:Sympatholytics / Q000008:administration & dosage; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D004745:Enkephalins; D018696:Neuroprotective Agents; D011498:Protein Precursors; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D013565:Sympatholytics; C036448:pre-prodynorphin; C081320:8-(3-chlorostyryl)caffeine; D002110:Caffeine; D004399:Dynorphins; D016627:Oxidopamine; C033660:preproenkephalin; D014446:Tyrosine 3-Monooxygenase