Inhibition of LTP in vivo by beta-amyloid peptide in different conformational states

• Published in: Brain research 2008-03, Vol.1197, p.135-142
• Main Authors: Schmid, Adrien W, Freir, Darragh B, Herron, Caroline E
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid beta-Peptides - administration & dosage; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - ultrastructure; Animals; Beta-amyloid peptide; Brain - drug effects; CA1 region; Congo Red; Hippocampus; In vivo; Injections, Intraventricular; Long-term potentiation; Long-Term Potentiation - drug effects; Male; Microscopy, Electron, Transmission; Neurology; Peptide Fragments - administration & dosage; Peptide Fragments - chemistry; Peptide Fragments - ultrastructure; Protein Structure, Secondary; Rats; Rats, Wistar; Synaptic Transmission - drug effects; Thiazoles
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2007.11.056

Abstract We have investigated changes in the morphological structure of Aβ1–40 during different incubation time periods at 37 °C ranging from 1 h to 7 days using Thioflavin T, Congo red binding and electron microscopy. We found distinctive changes in Aβ assembly demonstrating the formation of beta pleated sheets following 7-day incubation. Here we demonstrate that samples of the same Aβ1–40 peptide that are morphologically distinct can both attenuate hippocampal long-term potentiation (LTP) in the CA1 in vivo . The peptides were applied via intracerebroventricular injection and the effects on synaptic transmission, post-tetanic potentiation (PTP) and LTP were observed. The effects of Aβ1–40 that had either been freshly solubilized (FS-Aβ) or incubated at 37 °C for 7 days (7D-Aβ) were examined. FS-Aβ and 7D-Aβ peptide were both found to significantly attenuate LTP, although the assembly states of these peptides appeared to be completely different. Paired pulse facilitation (PPF) with an inter-stimulus interval of 50 ms was also monitored prior to, following peptide injection and 60 min following LTP induction. 7D-Aβ caused an increase in PPF prior to LTP induction and also depressed PTP. Our data demonstrate that, while both forms of the peptide can attenuate LTP, the fibrillar form of the peptide may also influence transmitter release.