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 L ，Yin WJ ，Zhang JF ，Qi JS ... -  《-》

Arginine vasopressin prevents amyloid beta protein-induced impairment of long-term potentiation in rat hippocampus in vivo.

Jing W ，Guo F ，Cheng L ，Zhang JF ，Qi JS ... -  《NEUROSCIENCE LETTERS》

Protein kinase C mediates amyloid beta-protein fragment 31-35-induced suppression of hippocampal late-phase long-term potentiation in vivo.

Zhang JF ，Qi JS ，Qiao JT 《-》

Amyloid beta-protein fragment 31-35 suppresses long-term potentiation in hippocampal CA1 region of rats in vivo.

Effects of fragment 31-35 of amyloid beta-protein (AbetaP31-35) on the baseline synaptic transmission, shown as fEPSPs, and the long-term potentiation (LTP) induced by high-frequency stimuli (HFS) were investigated in vivo in the hippocampal CA1 region of rats; a longer fragment of AbetaP, i.e., AbetaP25-35, which had been generally accepted as the active center in AbetaP, was also tested comparatively along with AbetaP31-35. The results showed that: (1) the baseline fEPSPs induced by test stimuli were not changed by i.c.v. injection of AbetaP31-35, while application of either AbetaP31-35 or AbetaP25-35 with the same molar concentration (50 nmol) significantly and similarly suppressed the HFS-induced LTP; (2) higher concentration of AbetaP31-35 or longer time of AbetaP exposure exhibited stronger suppression on LTP, indicating a dose- and time-dependent trends; (3) no significant effects could be found on the paired-pulse facilitation (PPF) following AbetaP31-35 injection; (4) pretreatment with verapamil (2.5 mg/kg, i.p., 1 h prior to HFS), a blocker of L-type Ca2+ channels, did not affect the baseline fEPSPs, while it exhibited a significant suppression on LTP induced by HFS; and (5) surprisingly enough, coapplication with verapamil and AbetaP31-35 exhibited a similar suppression on LTP just as both of these two agents were used alone. These results indicate that: (1) AbetaP31-35, similar to AbetaP25-35, possesses potent suppressive effects on hippocampal LTP in vivo, supporting our proposal that the fragment AbetaP31-35 might be to date the shortest active sequence in full-length of AbetaP molecule; (2) AbetaP31-35-induced LTP suppression is not mediated by affecting the presynaptic processes; and (3) L-type Ca2+ channels might be one of the main pathways by which AbetaP31-35 insults LTP.

Zhang JM ，Wu MN ，Qi JS ，Qiao JT ... -  《-》

The effects of IL-1 receptor antagonist on beta amyloid mediated depression of LTP in the rat CA1 in vivo.

Beta-amyloid (Abeta) is a neuro-peptide implicated in the pathogenesis of Alzheimer's disease (AD). Abeta-peptide is known to disrupt cellular processes, including synaptic plasticity. To date, the precise mechanisms leading to the Abeta-mediated impairment of normal neurophysiological function still remains elusive. A rise in the pro-inflammatory cytokine interleukin-1-beta (IL-1beta) has been previously reported, following Abeta peptide insult. IL-1beta in turn, activates a cascade of pro-apoptotic markers, gradually leading to cell death. In this work, we have investigated the possible protective effects of interleukin-1 receptor antagonist (IL-1ra) on the effects of Abeta-peptide on long-term potentiation (LTP) in the CA1 region of the rat hippocampus in vivo. We observed a significant depression of LTP in the group of animals that received intracerebroventricular (icv) injection of Abeta-peptide (1-40) compared with control animals injected with vehicle. Administration of IL-1ra alone (icv) also resulted in a depression of LTP; however, there was no change in the baseline synaptic response. Combined injection of Abeta(1-40) + IL-1ra caused an attenuation of the effects observed with Abeta(1-40) alone for a period of up to 15 min following LTP induction; rescuing post-tetanicpotentiation (PTP). Gradually however, EPSP-values declined to produce a level of LTP similar to that observed following treatment with Abeta(1-40) alone. These results suggest that the acute Abeta-mediated impairment of PTP and LTP may be partial as a result of activation of an inflammatory response and the release of IL-1beta. The attenuation of plasticity by IL-1ra alone supports the theory that low levels of IL-1beta are required for normal synaptic plasticity. The limited rescue of the Abeta-mediated effects on LTP, in the presence of IL-1ra, may represent the short half life found with this receptor antagonist in vivo.

Schmid AW ，Lynch MA ，Herron CE 《-》