title: Decreased vesicular acetylcholine transporter and alpha(4)beta(2) nicotinic receptor density in the rat brain following 192 IgG-saporin immunolesioning.
abstract: Degeneration of cholinergic neurons is a well known characteristic of Alzheimer's disease (AD). Two radioligands were studied in a rat model of cholinergic degeneration to evaluate their potential efficacy for molecular imaging of AD. Following specific cholinergic-cell immunolesioning with 192 IgG-saporin (SAP), ex vivo autoradiography was performed with (123)IBVM, a radioligand which targets the vesicular acetylcholine transporter (VAChT). Following the decay of (123)I, the same animals had in vitro autoradiography performed with (125)I-A-85380, a marker for nicotinic acetylcholine receptors (nAChRs). As expected significant, widespread decreases in (123)IBVM uptake were observed in SAP treated animals. Moderate but significant reductions in (125)I-A-85380 binding in the hippocampus (Hip) and cerebellum (Cbm) were also observed following SAP immunolesioning. The results with (123)IBVM confirm and extend previous work investigating the uptake of radioiodinated IBVM in this animal model. The results with (125)I-A-85380 are unique and are in contrast with work performed in this animal model with other nAChR radioligands, indicating the favourable properties of this radioligand for molecular imaging.
authors.affiliation: Universite Francois Rabelais de Tours, INSERM U619, Laboratoire de Biophysique Medicale et Pharmaceutique, 31 avenue Monge, 37200 Tours, France. mitchellq@med.usyd.edu.au
authors.forename: Mitchell
authors.initials: M
authors.lastname: Quinlivan
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chalon
authors.forename: Jackie
authors.initials: J
authors.lastname: Vergote
authors.forename: Jasmine
authors.initials: J
authors.lastname: Henderson
authors.forename: Andrew
authors.initials: A
authors.lastname: Katsifis
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.forename: Denis
authors.initials: D
authors.lastname: Guilloteau
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D001345:Autoradiography / Q000379:methods; D001384:Azetidines / Q000493:pharmacokinetics; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D000922:Immunotoxins / Q000633:toxicity*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D009699:N-Glycosyl Hydrolases / Q000633:toxicity*; D010880:Piperidines / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D018709:Statistics, Nonparametric; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism*
chemical_list: C085696:192 IgG-saporin; C104288:A 85380; D000911:Antibodies, Monoclonal; D001384:Azetidines; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D010880:Piperidines; D011978:Receptors, Nicotinic; D054789:Ribosome Inactivating Proteins, Type 1; D013764:Tetrahydronaphthalenes; D050494:Vesicular Acetylcholine Transport Proteins; C403531:nicotinic receptor alpha4beta2; C065043:5-iodobenzovesamicol; D009699:N-Glycosyl Hydrolases; D000076985:Saporins