Amyloid beta-protein fragments 25-35 and 31-35 potentiate long-term depression in hippocampal CA1 region of rats in vivo.
Amyloid beta-protein (Abeta) 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 Abeta fragments suppress the long-term potentiation (LTP) of synaptic transmission. However, it is unclear whether Abeta fragments can regulate long-term depression (LTD), an equally important form of synaptic plasticity in the brain. The present study investigates the effects of Abeta 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 Abeta fragment 25-35 (Abeta(25-35), 12.5 and 25 nmol) did not change baseline field excitatory postsynaptic potentials but dose-dependently potentiated LTD; (4) Abeta fragment 31-35 (Abeta(31-35)), a shorter Abeta fragment than Abeta(25-35), also dose-dependently strengthened LFS-induced hippocampal LTD. Thus, the present study demonstrates the enhancement of hippocampal LTD by Abeta in in vivo condition. We propose that Abeta-induced potentiation of LTD, together with the suppression of LTP, will result in the impairment of cognitive function of the brain.
Cheng
Li
L
Department of Neurobiology, Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China.
Yin
Wen-Juan
WJ
Zhang
Jun-Fang
JF
Qi
Jin-Shun
JS
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001703:Biophysics; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects*; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C113042:amyloid beta-protein (31-35)