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

Abstract

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.