Effects of Aβ1-42 fibrils and of the tetrapeptide Pr-IIGL on the phosphorylation state of the τ-protein and on the α7 nicotinic acetylcholine receptor in vitro

Enzo Lain, Botond Penke, André Delacourte, Daniela Gündisch, Hannsjörg Schröder, Brigitte Witter

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Abstract

In order to investigate the possible links connecting β-amyloid (Aβ) accumulation, τ-hyperphosphorylation and nicotinic receptor expression, rat embryonic primary hippocampal cultures were incubated with amyloidogenic peptides. Exposure to 0.5 μM fibrillar Aβ1-42 for 3 days caused retraction of dendrites, shrinkage of cell bodies and a decrease in the expression of microtubule-associated proteins 2b (MAP2b), without affecting the total number of neurons and their viability. No impact on the τ-phosphorylation sites Ser-202, Thr231/Ser235, Ser262 and Ser396/Ser404 was found. The total number of homomeric α7-nicotinic receptors (α7-nAChRs) and their affinity for [125I]α-bungarotoxin remained unaltered. Upon incubation with the putatively protective tetrapeptide propionyl-isoleucine-isoleucine-glycine-leucine (Pr-IIGL), an analogue of the region [31-34] of Aβ, cell bodies were swollen in the region of the apical dendrite. These morphological alterations, different from those elicited by Aβ1-42, did not involve MAP2 expression changes. In contrast to Aβ1-42, Pr-IIGL caused a massive hyperphosphorylation of the τ-protein at Ser-202 and at Ser396/Ser404. The total number of homomeric α7-nAChRs and their affinity for [125I]α-bungarotoxin were unaffected. In conclusion, the present results show a toxic effect of Aβ1-42 on the cytoskeletal structure at concentrations normally present in the brains of Alzheimer's disease patients, but raise some doubts about the role of Aβ1-42 fibrils as a direct trigger of τ-hyperphosphorylation. The tetrapeptide Pr-IIGL cannot be considered protective with regard to cell morphology. Although it prevents the Aβ1-42-induced retraction of dendrites, it exhibits other toxic properties. The homomeric α7-nAChRs were not affected either by Aβ1-42 incubation or by Pr-IIGL-induced τ- hyperphosphorylation.

Original languageEnglish
Pages (from-to)879-888
Number of pages10
JournalEuropean Journal of Neuroscience
Volume21
Issue number4
DOIs
Publication statusPublished - Feb 1 2005

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Keywords

  • Bungarotoxin
  • Hippocampus dissociation culture
  • Immunocytochemistry
  • Rat
  • Western blot

ASJC Scopus subject areas

  • Neuroscience(all)

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