Neuroscience 2005 Abstract
| Presentation Number: | 910.3 |
|---|---|
| Abstract Title: | A novel phospholipid-based drug formulation inhibits the acute and chronic effects of β-amyloid administration on long-term potentiation and microglia activation in rat hippocampus. |
| Authors: |
Miller, A.*1
; Piazza, A.1
; Walsh, M.1,2
; Martin, D. S. D.1,2
; Mandel, A.
; Bolton, A.2
; Lynch, M. A.1
1Physiology Dept., Trinity Inst. of Neuroscience, Trinity Col. Dublin, Dublin, Ireland 2Ireland, Department of Physiology, Trinity Institute of Neuroscience, Dublin, Ireland., Dublin 2, |
| Primary Theme and Topics |
Disorders of the Nervous System - Neurotoxicity, Inflammation, and Neuroprotection -- Neuroinflammation |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Neurotoxicity, Inflammation, and Neuroprotection<br />-- Neuroprotective mechanisms and treatments |
| Session: |
910. Neuroinflammation: Age Related Poster |
| Presentation Time: | Wednesday, November 16, 2005 10:00 AM-11:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # UU19 |
| Keywords: | INFLAMMATION, INTERLEUKIN 1BETA, LTP, HIPPOCAMPUS |
VP025 (Vasogen Inc.) is a preparation of phospholipid microparticles containing phosphatidylglycerol, shown to exert anti-inflammatory effects in brain and to abrogate lipopolysaccharide- and age-induced up-regulation of IL-1β and IL-1β-induced signalling (Martin et al.,SFN abstracts 2004, 904.8). Here we assessed the effect of VP025 on changes induced by a single intracerebroventricular injection and chronic administration of β-amyloid. In one study, groups of 8 young male Wistar rats were injected intramuscularly with either 150µl of saline or VP025 (1.2 x 107 particles/ml) on days 14, 13 and 1 before assessing their ability to sustain long-term potentiation (LTP). On day 0, urethane-anaesthetized rats were injected intracerebroventricularly (icv) with (5µl) saline or β-amyloid (200µM), and 3 hours later were assessed for LTP in perforant path-granule cell synapses. In a second study, groups of 6 rats were similarly pre-treated with saline or VP025. These animals were anaesthetized to allow implantation of Alzet minipumps and then chronically infused icv with a combination of β-amyloid 1-40 and 1-42 (26.9 and 36.9µM respectively) or control peptide, β-amyloid 40-1 (63.8µM) for 8 days prior to LTP assessment. In both studies, rats were sacrificed and tissue taken for later analysis. Both acute and chronic β-amyloid treatment led to impairment of LTP, this impairment was abrogated in both cases by prior administration of VP025. Microglial activation, as assessed by MHCII expression, and IL-1β concentration were increased in hippocampus of amyloid-β-treated rats and these changes were abrogated by VP025. The findings support earlier observations which demonstrate an anti-inflammatory and neuroprotective effect of VP025.
Supported by A-M Miller is a post-graduate student funded by Vasogen Ireland Ltd.
<B>Conflict of Interest:</B> This work is funded by Vasogen Ireland Limited.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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