Alzheimer's disease and Down syndrome rodent models exhibit audiogenic seizures.
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.
Westmark
Cara J
CJ
Department of Pathology & Laboratory Medicine and Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI 53705, USA. westmark@wisc.edu
Westmark
Pamela R
PR
Malter
James S
JS
D000161:Acoustic Stimulation; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000276:immunology; D000818:Animals; D003292:Convulsants; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics; D020195:Epilepsy, Reflex / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D007116:Immunization, Passive; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010433:Pentylenetetrazole; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D012640:Seizures / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D003292:Convulsants; D051860:Fragile X Messenger Ribonucleoprotein 1; D010433:Pentylenetetrazole; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C578936:Grm5 protein, mouse