title: Effects of amyloid-beta on cholinergic and acetylcholinesterase-positive cells in cultured basal forebrain neurons of embryonic rat brain.
abstract: The neurotoxic effects of amyloid-beta(1-42) and amyloid-beta(25-35) (A beta) on cholinergic and acetylcholinesterase-positive neurons were investigated in primary cultures derived from embryonic 18-day-old rat basal forebrain. After various time intervals, the cultures were treated with 1, 5, 10 or 20 microM A beta for different time periods. The cholinergic neurons and their axon terminals were revealed by vesicular acetylcholine transporter immunohistochemistry and the cholinoceptive cells by acetylcholinesterase histochemical staining. To assess the toxic effects of these A beta peptides on the cholinergic neurons, image analysis was applied for quantitative determination of the numbers of axon varicosities/terminals and cells. The results demonstrate that, following treatment with 1 or 5 microM A beta for 5, 10, 30, 60 or 120 min, no changes in vesicular acetylcholine transporter immunohistochemical staining were observed. However, after treatment for 30 min with 10 or 20 microM A beta, the number of stained axon varicosities was reduced, and treatment for 2 h they had disappeared. In contrast, vesicular acetylcholine transporter-positivity could be seen in some of the neuronal perikarya even after 3 days after treatment. The acetylcholinesterase staining was homogeneously distributed in the control neurons. After A beta treatment, the histochemical reaction end-product was detected in some of the neuronal perikarya or in the dendritic processes near to the soma. It is concluded that the neurotoxic effects of A beta appear more rapidly in the cholinergic axon terminals than in the cholinergic and acetylcholinesterase-positive neuronal perikarya.
authors.affiliation: Alzheimer's Disease Research Centre, Department of Psychiatry, University of Szeged, Somogyi B. ut 4., Szeged H-6720, Hungary. kp@comser.szote.u-szeged.hr
authors.forename: Peter
authors.initials: P
authors.lastname: Kasa
authors.forename: Henrietta
authors.initials: H
authors.lastname: Papp
authors.forename: Peter
authors.initials: P
authors.lastname: Kasa
authors.forename: Magdolna
authors.initials: M
authors.lastname: Pakaski
authors.forename: Lajos
authors.initials: L
authors.lastname: Balaspiri
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D007150:Immunohistochemistry; D026901:Membrane Transport Proteins; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000633:toxicity; D016548:Prosencephalon / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
chemical_list: D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D010446:Peptide Fragments; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; C075222:amyloid beta-protein (1-42); C439320:amyloid beta-protein (25-36); D000110:Acetylcholinesterase; D000109:Acetylcholine