Stimulus pattern dependence of the Alzheimer's disease amyloid-beta 42 peptide's inhibition of long term potentiation in mouse hippocampal slices.
Increasing evidence has pointed to inhibition of Long Term Potentiation (LTP) by soluble A beta 42 oligomers as central in the etiology of the learning and memory deficits that are hallmarks of Alzheimer Disease. These effects are thought to occur by an interaction between A beta 42 and certain cellular effectors that induce LTP, however, the precise identity of the A beta 42-interactive signaling molecules is unknown. Identification of such effectors is made more difficult because LTP induced by different stimulation protocols can be expressed through heterogeneous signaling pathways. The aim of this study was to compare differences in the A beta 42-dependent levels of inhibition of LTPs that were induced using high frequency stimulation (HFS), versus theta burst stimulation (TBS). Our results show that untreated control brain slices tetanized with either HFS or TBS gave similar levels of LTP and post tetanic stimulation (PTP), suggesting that the response induced by either protocol was comparable. However, A beta 42 peptide significantly blocked LTP and PTP induced by HFS, but not when TBS was used. NMDA receptor antagonists, D-AP5 and ifenprodil, both blocked LTPs that were induced by HFS or TBS. We propose that unknown signaling effectors, other than the NMDA receptor, which are differentially involved in the induction of LTP by TBS, as compared to HFS, may be responsible for this resistance of TBS-induced LTP to A beta 42 dependent inhibition.
Smith
Jeffrey P
JP
Colorado State University-Pueblo, Pueblo, CO 81001, USA. jeff.smith@colostate-pueblo.edu
Lal
Varsha
V
Bowser
David
D
Cappai
Roberto
R
Masters
Colin L
CL
Ciccotosto
Giuseppe D
GD
D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000502:physiology*; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012995:Solubility
D016229:Amyloid beta-Peptides; D018691:Excitatory Amino Acid Antagonists; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)