Neuroscience 2001 Abstract
| Presentation Number: | 860.16 |
|---|---|
| Abstract Title: | APP OVEREXPRESSION IMPAIRS EYEBLINK CONDITIONING & DECREASES HIPPOCAMPAL VOLUME IN MICE. |
| Authors: |
Weiss, C.*1
; Aguado, A. S.1
; Venkatasubramanian, P. N.2
; Power, J. M.1
; Li, L.2
; Chen, K. S.3
; Wyrwicz, A. M.2
; Disterhoft, J. F.1
1Cell & Mol.Bio., Northwestern Univ., Chicago, IL 2ENH Research Institute, Evanston, IL 3Elan Pharmaceuticals, S. San Francisco, CA |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Neurodegenerative Disorders -- Alzheimers Disease: APP, presenilin and secretases |
| Secondary Theme and Topics | Neurological and Psychiatric Conditions<br />- Genetic Models |
| Session: |
860. Neurodegenerative disorders: Alzheimer's disease--A-beta and animal models III Poster |
| Presentation Time: | Wednesday, November 14, 2001 4:00 PM-5:00 PM |
| Location: | Exhibit Hall VV-50 |
| Keywords: | AMYLOID PRECURSOR PROTEIN, CLASSICAL CONDITIONING, HIPPOCAMPUS, IMAGING |
We examined heterozygous transgenic (Tg) mice that overexpress V717F amyloid precursor protein (APP) for behavioral learning with eyeblink conditioning, and for hippocampal volume with magnetic resonance imaging (MRI). Mice (6 or 10m of age) were conditioned to blink by pairing a 350 ms flash of light with a 100 ms coterminating periorbital shock. A significant increase in eyelid EMG activity prior to the shock defined a conditioned response (CR). Mice that exhibited 7 CRs within any block of 10 consecutive trials were considered learners. Our results indicate that a significant proportion of transgenic mice were impaired relative to age-matched wild type (WT) controls. While 75% of WT mice learned by day 6 (90% by day 12), only 20% of Tg mice learned by day 6 (30% by day 12). The same mice were examined with MRI 4 months after behavioral training. T2-weighted spin echo images (62.5 x 125 x 500 µm) were taken from anesthetized mice using a 9.4T vertical bore magnet. The number of pixels comprising the hippocampus, and the contrast to noise ratios (CNR) of the cortex, hippocampus, and subcortical region were measured. Our results indicate that the hippocampus of Tg mice was 27% smaller than that of WT mice. There were no significant differences in the CNR between groups or across regions. These results indicate that APP or A-beta overexpression has profound effects on learning and memory, and hippocampal volume; and that cognitive deficits precede the age at which amyloid plaques are expected to occur.
Supported by NUADC, NUDDP, IL PHS, AG015511, Alzheimer's Assoc.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2001 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2001. Online.
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