Increased seizure threshold and severity in young transgenic CRND8 mice.
Reports suggest that Alzheimer's disease (AD) patients show a high life-time prevalence of seizure-like disorders. The transgenic CRND8 (TgCRDN8) is a mouse model of AD-like amyloid pathogenesis that expresses a double-mutant form of human amyloid precursor protein 695 (K670N/M671L and V717F). We have previously reported that post-plaque TgCRND8 mice exhibited a lower threshold to seizure with a more severe seizure type when challenged with pentylenetetrazole (PTZ) intravenously. Here, we now report that pre-plaque TgCRND8 mice also demonstrate an increased sensitivity to PTZ-induced seizures with a more severe seizure type over age-matched littermate controls. A lower threshold and more severe seizure type in TgCRND8 mice prior to and after plaque deposition suggest that this genotype difference may be due to beta-amyloid (Abeta) toxicity rather than plaque formation. Thus, the TgCRND8 mice are not only a model for Abeta production and plaque deposition, but may also be useful for AD associated seizure.
CNS Biological Research, K-15/2600, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. Robert.delvecchio@spcorp.com
Robert A
RA
Del Vecchio
Lisa H
LH
Gold
Steve J
SJ
Novick
Gwen
G
Wong
Lynn A
LA
Hyde
D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D012684:Sensory Thresholds / Q000502:physiology*; D018709:Statistics, Nonparametric
D016564:Amyloid beta-Protein Precursor; D010433:Pentylenetetrazole