Publikationsdatenbank

Acetylcholine receptor binding and cholinergic interneuron density are unaltered in a genetic animal model of primary paroxysmal dystonia (2006)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Hamann, Melanie

Raymond, Roger

Varughesi, Suneel

Nobrega, José N

Richter, Angelika

Quelle

Brain research; 1099(1) — S. 176–182

ISSN: 0006-8993

Sprache

Englisch

Verweise

Pubmed: 16764832

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

The underlying pathophysiological mechanisms of hereditary types of paroxysmal dyskinesias are still unknown, but basal ganglia dysfunctions seem to play a critical role. In fact, numerous pharmacological, neurochemical, immunohistochemical and electrophysiological investigations in the dt(sz) hamsters, a unique rodent model of age-dependent primary paroxysmal dystonia, revealed alterations within the basal ganglia, particularly of the GABAergic and dopaminergic neurotransmitter systems. A deficit in several types of striatal GABAergic interneurons in dt(sz) mutant hamsters seems to play a crucial pathophysiological role, but deficits in other types of striatal interneurons cannot be excluded by previous studies. In view of ameliorating effects of anti-cholinergic drugs in dystonic patients, we therefore investigated the density of striatal cholinergic interneurons in the present study. These interneurons were marked specifically by the enzyme choline acetyltransferase and counted by using a stereological counting method in a blinded fashion. Additionally, acetylcholine receptor binding was determined in mutant and nondystonic control hamsters by autoradiographic analyses with the nonselective muscarinic ligand [(3)H]-quinuclidinyl benzilate (QNB) in 11 brain (sub)regions. There were no significant differences in the density of striatal cholinergic interneurons between dt(sz) mutant hamsters (789 +/- 39 interneurons/mm(3)) and nondystonic controls (807 +/- 36 interneurons/mm(3)). [(3)H]QNB binding was also comparable between mutant and control hamsters. These results point to an unaltered striatal cholinergic neurotransmitter system in dt(sz) hamsters under basal conditions.