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Neuroprotection, Neurotoxicity and Neuroinflammation

開催日 2014/9/13
時間 16:00 - 17:00
会場 Room I(311+312)
Chairperson(s) 丸山 和佳子 / Wakako Maruyama (独立行政法人国立長寿医療研究センター 加齢健康脳科学研究部 / Department of Cognitive Brain Science, National Center for Geriatries and Gerontology, Japan)
澤田 誠 / Makoto Sawada (名古屋大学 環境医学研究所 / Research Institute of Environmental Medicine, Nagoya University, Japan)

Voltage-sensitive dye imaging of whole hippocampal circuit activity showing alteration in excitability after maternal bisphenol A exposure in mice

  • O3-I-4-1
  • 冨永 貴志 / Takashi Tominaga:1 冨永 洋子 / Yoko Tominaga:1 五十嵐 勝秀 / Katsuhide Igarashi:2,3 大塚 まき / Maky I Otsuka:2,3 古川 佑介 / Yusuke Furukawa:2 菅野 純 / Jun kanno:2 種村 健太郎 / Kentaro Tanemura:4 
  • 1:徳島文理大学 / Inst Neurosci, Tokushima Bunri University, Kagawa, Japan 2:国立医薬品食品衛生研・安全性生物試験研究センター・毒性部 / Div Cellular & Molecular Toxicol, NIHS, Tokyo, Japan 3:先端生命科学研究所・先端生命科学研究センター(L-StaR)・星薬科大学 / L-StaR, Hoshi University, Sch Pharm Pharmaceut Sci, Tokyo, Japan 4:東北大院・農・動物生殖科学 / Lab Animal Reproduction, Grad Sch Agr Sci, Tohoku Univ., Sendai, Japan 

There are increasing concerns about disruption of brain function due to exposure to environmental chemical substances, especially in the early stages of development. We aimed to develop a method to assess such effects on neuronal circuit activity. Bisphenol A (BPA), which is widely used in the production of polycarbonate plastics and epoxy resins, is a potentially hazardous chemical substance. BPA can bind estrogen receptors and affect the signal cascade of endogenous estradiol. A number of reports have indicated that estrogen affects synaptic plasticity in the hippocampal (HP) circuit in rats and mice. Pairs of male and female mice were transferred for mating into cages where we supplied BPA-containing drinking water at four different concentrations (0, 0.1, 1, and 10 ppm). On confirmation of pregnancy, BPA-containing drinking water was supplied until weaning. Male offspring were randomly chosen from mothers maintained under the same conditions. Hippocampal slices were made by standard procedures and analyzed after staining with voltage-sensitive dye (VSD: Di-4-ANEPPS) after at least 8 weeks. Stimulation of three main pathways of the HP, the perforant (PP), mossy fiber (MF), and Schaffer collateral pathways (Sch), was studied using the VSD imaging assay. The neuronal responses of the control (0 ppm) and BPA-exposed mice (0.1, 1 and 10 ppm BPA) were tested in normal and Gabazine (10 μM)-containing ACSF. Gabazine increased the peak amplitude and duration of the response to strong stimulation in both control and BPA-exposed mice. In control mice, even very weak stimulation was sufficient to induce large and long responses in the entire CA3-CA1, whereas BPA-exposed mice did not exhibit such responses. The clear difference may indicate a difference in the threshold of excitability of the cells. These results highlight the use of VSD imaging assay to assess environmental risk factors.

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