The Effects of IL-1 Receptor Antagonist on Beta Amyloid Mediated Depression of LTP in the Rat CA1 In Vivo

Beta-amyloid (A beta) is a neuro-peptide implicated in the pathogenesis of Alzheimer's disease (AD). A beta-peptide is known to disrupt cellular processes, including synaptic plasticity. To date, the precise mechanisms leading to the A beta-mediated impairment of normal neurophysiological function still remains elusive. A rise in the pro-inflammatory cytokine interieukin-1-beta (IL-1 beta) has been previously reported, following A beta peptide insult. IL-1 beta 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 A beta-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 A beta-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 A beta(1-40) + IL-1ra caused an attenuation of the effects observed with A beta(1-40) alone for a period of up to 15 min following LTP induction; rescuing post-tetanic potentiation (PTP). Gradually however, EPSP-values declined to produce a level of LTP similar to that observed following treatment with A beta(1-40) alone. These results suggest that the acute A beta-mediated impairment of PTP and LTP may be partial as a result of activation of an inflammatory response and the release of IL-1 beta. The attenuation of plasticity by IL-1ra alone supports the theory that low levels of IL-1 beta are required for normal synaptic plasticity. The limited rescue of the A beta-mediated effects on LTP, in the presence of IL-1ra, may represent the short half life found with this receptor antagonist in vivo. (C) 2008 Wiley-Liss, Inc.