Soy-based diet exacerbates seizures in mouse models of neurological disease

Cara J. Westmark, Pamela R. Westmark, James S. Malter

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)797-805
Number of pages9
JournalJournal of Alzheimer's Disease
Volume33
Issue number3
DOIs
StatePublished - 2013

Fingerprint

Neurological Models
Seizures
Diet
Amyloid beta-Protein Precursor
Soybean Proteins
Isoflavones
Genistein
Running
Alzheimer Disease
Phenotype
Fragile X Syndrome
Down Syndrome
Caseins
Nervous System Diseases
Amyloid
daidzein
Rodentia
Neurons
Mortality

Keywords

  • amyloid β-protein precursor
  • Amyloid-β
  • daidzein
  • isoflavone
  • seizure
  • soy

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Soy-based diet exacerbates seizures in mouse models of neurological disease. / Westmark, Cara J.; Westmark, Pamela R.; Malter, James S.

In: Journal of Alzheimer's Disease, Vol. 33, No. 3, 2013, p. 797-805.

Research output: Contribution to journalArticle

Westmark, Cara J. ; Westmark, Pamela R. ; Malter, James S. / Soy-based diet exacerbates seizures in mouse models of neurological disease. In: Journal of Alzheimer's Disease. 2013 ; Vol. 33, No. 3. pp. 797-805.
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