title: Soy-based diet exacerbates seizures in mouse models of neurological disease.
abstract: Seizures are a common phenotype in many neurological disorders including Alzheimer's disease, Down syndrome, and fragile X syndrome. Mouse models of these disorders overexpress amyloid-β protein precursor (AβPP) and amyloid-β (Aβ) and are highly susceptible to audiogenic-induced seizures (AGS). We observed decreased AGS in these mice fed a casein-based, purified diet (D07030301) as opposed to a standard soy protein-containing, non-purified diet (Purina 5015). Our objective in this manuscript was to determine if soy protein, and in particular soy isoflavones, in the Purina 5015 were contributing to the seizure phenotype. Wild running, AGS, and death rates were assessed in juvenile mice fed Purina 5015, D07030301, D07030301 containing soy protein, or D07030301 supplemented with individual isoflavones (750 mg/kg daidzein or genistein). A short treatment (3 days) with Purina 5015 induced wild running and AGS in Alzheimer's disease mice. A 3-day treatment with daidzein-supplemented diet, but not genistein, induced wild running in wild type mice. To understand the mechanism underlying daidzein activity, we assessed dendritic AβPP expression in primary, cultured, wild type neurons treated with daidzein or genistein. In vitro, daidzein significantly increased dendritic AβPP. Thus, the soy isoflavone daidzein recapitulated seizure induction in vivo and altered AβPP expression in vitro. These results have important implications for individuals on soy-based diets as well as for rodent model research.
authors.affiliation: Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI 53705, USA. westmark@wisc.edu
authors.forename: Cara J
authors.initials: CJ
authors.lastname: Westmark
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Westmark
authors.forename: James S
authors.initials: JS
authors.lastname: Malter
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004032:Diet; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D006801:Humans; D008124:Locomotion / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009422:Nervous System Diseases / Q000150:complications* / Q000235:genetics / Q000401:mortality; D011247:Pregnancy; D053764:Presenilin-1 / Q000235:genetics; D012640:Seizures / Q000178:diet therapy / Q000209:etiology*; D030262:Soybean Proteins / Q000009:adverse effects* / Q000737:chemistry
chemical_list: D016564:Amyloid beta-Protein Precursor; D051860:Fragile X Messenger Ribonucleoprotein 1; D053764:Presenilin-1; D030262:Soybean Proteins; C497684:Fmr1 protein, mouse; C508853:PSEN1 protein, human