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2017 | 77 | Suppl.1 |
Tytuł artykułu

Dietary hyperhomocysteinemia reduces brain AQP4 expression and cognitive performance in old mice

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INTRODUCTION: Elevated plasma total homocysteine (tHcy), i.e. hyperhomocysteinemia (HHcy), is associated with brain pathologies such as vascular dementia, cognitive decline and Alzheimer’s disease and glial functions. Learning and memory may also be indirectly regulated by water homeostasis in the brain. AIM(S): Determine how the mouse brain and behaviour are affected by chronic long‑term dietary HHcy. METHOD(S): HHcy was induced in 8-month-old C57BL/6 male mice by providing 1% methionine in drinking water for 12 months. Control mice did not receive methionine. At 20 months of age, weight, urinary tHcy, and behavioural phenotypes were recorded. Cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Mice were sacrificed, perfused, and brains were collected for aquaporin‑4 (AQP4) immunohistochemistry. RESULTS: HHcy mice had lower body weight than controls (31.4±1.1 vs. 35.1±1.3 g, p=0.04). HHcy mice had 32-fold higher urinary tHcy than controls (493±57 vs. 15.3±4.9 μM, p<0.0001). HHcy mice showed neurodegener ing and spatial orientation in Kcnb1 mutant embryos and larvae. RESULTS: The otic vesicle and otoliths of Kcnb1 mutant develop relatively normal. We observed significant length reduction of the otic vesicle in mutant embryos. Mutants demonstrate significant hearing defects and uncoordinated balance movements. CONCLUSIONS: Unlike clear morphological abnormality of the brain ventricular system, development of the otic vesicle in Kcnb1 zebrafish mutant is relatively uneventful. Kcnb1 requirement in the ear manifests itself in mutants as abnormal hearing and vestibular function. FINANCIAL SUPPORT: This work was supported by funds from OPUS grant to Vladimir Korzh from National Science Centre (OPUS UMO-2016/21/B/N23/00354).
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  • Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, Poznan, Poland
  • Laboratory of Neurobiology, Department of Veterinary Medicine and Animal Sciences, Poznan University of Life Sciences, Poznan, Poland
  • Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, Poznan, Poland
  • Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School, International Center for Public Health, Newark, USA
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