Alzheimer's disease and Down syndrome rodent models exhibit audiogenic seizures - PubMed (original) (raw)

Alzheimer's disease and Down syndrome rodent models exhibit audiogenic seizures

Cara J Westmark et al. J Alzheimers Dis. 2010.

Abstract

Amyloid-beta protein precursor (AbetaPP) is overexpressed in Alzheimer's disease (AD), Down syndrome (DS), autism, and fragile X syndrome. Seizures are a common phenotype in all of these neurological disorders, yet the underlying molecular mechanism(s) of seizure induction and propagation remain largely unknown. We demonstrate that AD (Tg2576) and DS (Ts65Dn) mice exhibit audiogenic seizures, which can be attenuated with antagonists to metabotropic glutamate receptor 5 (mGluR5) or by passive immunization with anti-amyloid-beta antibody. Our data strongly implicates AbetaPP or a catabolite in seizure susceptibility and suggests that mGluR5 mediates this response.

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Figures

Figure 1

Figure 1

WR, AGS and Death Rates in WT, fmr-1-/-, Tg2576, FRA×AD and Ts65Dn Mice. Mice (age P21) were exposed to 118 dB siren and the percentage exhibiting WR, AGS and death was plotted versus genotype for WT (Wt, n=39), fmr-1-/- (Fm, n=16), Tg2576 (Tg, n=16), FRA×AD (Fr, n=24), littermate controls for Ts65Dn (Cn, n=13), and Ts65Dn (Ds, n=16). All mice were in a C57BL/6 background except for Ts65Dn and littermates, which were in a mixed background. Statistically significant differences between Tg2576 or FRA×AD compared with WT and between Ts65Dn and littermate controls were assessed by Chi Square analyses (*) (p<0.03).

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