Amyloid β-protein fragments 25-35 and 31-35 potentiate long-term depression in hippocampal CA1 region of rats in vivo

• Published in: Synapse (New York, N.Y.) Vol. 63; no. 3; pp. 206 - 214
• Main Authors: Cheng, Li, Yin, Wen-Juan, Zhang, Jun-Fang, Qi, Jin-Shun
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2009
• Subjects: Alzheimer's disease; Amyloid beta-Peptides - pharmacology; Animals; Biophysics; Dose-Response Relationship, Drug; Electric Stimulation; field excitatory postsynaptic potentials; Hippocampus - drug effects; Long-Term Synaptic Depression - drug effects; Male; Peptide Fragments - pharmacology; Rats; Rats, Wistar; synaptic plasticity
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/syn.20599

Amyloid β‐protein (Aβ) is thought to be responsible for the deficit of learning and memory in Alzheimer's disease (AD), possibly through interfering with synaptic plasticity in the brain. It has been reported that Aβ fragments suppress the long‐term potentiation (LTP) of synaptic transmission. However, it is unclear whether Aβ fragments can regulate long‐term depression (LTD), an equally important form of synaptic plasticity in the brain. The present study investigates the effects of Aβ fragments on LTD induced by low frequency stimulation (LFS) in the hippocampus in vivo. Our results showed that (1) prolonged 1–10 Hz of LFS all effectively elicited LTD, which could persist for at least 2 h and be reversed by high frequency stimulation (HFS); (2) the effectiveness of LTD induction depended mainly on the number of pulses but not the frequency of LFS; (3) pretreatment with Aβ fragment 25–35 (Aβ25–35, 12.5 and 25 nmol) did not change baseline field excitatory postsynaptic potentials but dose‐dependently potentiated LTD; (4) Aβ fragment 31–35 (Aβ31–35), a shorter Aβ fragment than Aβ25–35, also dose‐dependently strengthened LFS‐induced hippocampal LTD. Thus, the present study demonstrates the enhancement of hippocampal LTD by Aβ in in vivo condition. We propose that Aβ‐induced potentiation of LTD, together with the suppression of LTP, will result in the impairment of cognitive function of the brain. Synapse 63:206–214, 2009. © 2008 Wiley‐Liss, Inc.