Beta-amyloid blocks high frequency stimulation induced LTP but not nicotine enhanced LTP.
Nicotine has been postulated to be a possible neuroprotective agent in Alzheimer's Disease (AD). In the present studies, the effect of beta-amyloid (Abeta) was investigated on the nicotine enhancement of high-frequency-induced LTP. Perfusion of nicotine substantially enhanced HFS-induced LTP in both rat and mouse dentate gyrus. The enhancing action of nicotine was mediated via alpha7 nAChRs as it was absent in mice null for alpha7 nAChR. Abeta strongly inhibited the induction of LTP in control animals, with LTP being completely inhibited at 1h post-HFS. Although Abeta also inhibited LTP in the presence of nicotine, the extent of the inhibition of LTP in nicotine perfused slices was similar to that in control, resulting in substantial LTP remaining in the presence of Abeta in the nicotine perfused slices. The nicotine enhanced LTP and the LTP remaining in the presence of Abeta and nicotine, although not the control LTP was dependent on activation of PKA. Chronic nicotine treatment also enhanced HFS-LTP recorded in acute slices taken from the nicotine-treated animals, and such LTP was only partially inhibited by Abeta. We postulate that nicotine-enhanced LTP has certain different mechanisms to that of control LTP which results in a resistance to inhibition by Abeta.
Welsby
Philip J
PJ
Department of Physiology, Trinity College, Dublin 2, Ireland. welsbyp@tcd.ie
Rowan
Michael J
MJ
Anwyl
Roger
R
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology*; D007546:Isoquinolines / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects* / Q000528:radiation effects; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology
D016229:Amyloid beta-Peptides; C402445:Chrna9 protein, mouse; D007546:Isoquinolines; D011978:Receptors, Nicotinic; D013449:Sulfonamides; D009538:Nicotine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide