演題詳細
Oral
アルツハイマー病、他の認知症、老化 4
Alzheimer's Disease, Other Dementia, Aging 4
| 開催日 | 2014/9/12 |
|---|---|
| 時間 | 16:00 - 17:00 |
| 会場 | Room I（311+312） |
| Chairperson(s) | 古川 勝敏 / Katsutoshi Furukawa (東北大学加齢医学研究所老年医学分野 / Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development Aging and Cancer, Tohoku University, Jap) 遠山 育夫 / Ikuo Tooyama (滋賀医科大学分子神経科学研究センター / Molecular Neuroscience Research Center, Shiga University of Medical Science, Japan) |
糖尿病モデルにおけるリン酸化タウと神経炎症の脳内分布
Regional Distribution of Microglial Proliferation and Tau Phosphorylation in Diabetes Mellitus Model of Tauopathy
- O2-I-4-4
- 本井 ゆみ子 / Yumiko Motoi:1 ハッサン ザフラル / Zafrul Hassan:3 松本 信英 / Shin-Ei Matsumoto:1,2 石黒 幸一 / Koichi Ishiguro:2 服部 信孝 / Nobutaka Hattori:1,2
- 1:順天堂大学医学部大学院 認知症診断・予防・治療学講座 / Dept Diagnosis, Prevention and Treatment of Dementia, Juntendo University School of Medicine, Japan 2:順天堂大学脳神経内科 / Dept Neurology, Juntendo University School of Medicine, Japan 3:順天堂大学スポトロジーセンター / Spotology center, Juntendo University School of Medicine, Japan
Purpose>Diabetes mellitus (DM) is a risk factor of Alzheimer's disease. It was shown that hyperglycemia or lack of insulin induced tau hyperphosphorylation and neuroinflammation. We examined the two alterations using various brain regions of DM model of tauopathy.
Methods> Experimental DM mice were generated through Intraperitoneal (60mg/kg) injection of streptozotocin (STZ) in 16-month-old female Tg601 (Neurobiol Dis 42, 404,2011)and non-transgenic (NT)mice for 5 consecutive days (n = 8, respectively). Control female Tg601 and NT mice were injected with 0.9% saline (n = 8, respectively). Twenty-two days later, mice were sacrificed followed by behavioral analysis by cervical dislocation, and brains were immediately removed. Three tasks including forced swimming test(FST)were evaluated. For biochemical analysis, Brains were dissected to multiple brain regions including the olfactory bulb, frontal cortex, septum, striatum, cerebellum, medulla, hippocampus, temporal cortex, thalamus, and brain stem. Each part of the brain was dissolved in TBS and the soluble fraction of tau as supernatant (S1) was collected. The following antibodies were used: phosphorylation-independent antibody, AT8, AT180 and pS396, phosphorylation-dependent antibody, TauC, IL-1Β, IL-6, TNF, IL-10 and Iba1.
Results> The immobility time of FST was decreased in STZ-treated mice. In Tg601 mice, STZ treatment increased tau phosphorylation, recognized by AT8 and AT180 antibodies in the striatum and hippocampus compared to saline treatment while phosphorylated tau elevation was not observed in the cerebellum. NT mice also demonstrated the same tendency of STZ -induced tau hyperphosphorylation. In the striatum and hippocampus, the number of Iba1-positive microglia was higher in STZ-treated Tg601 mice than saline-treated mice, whereas the cerebellum and midbrain did not show the difference.
Conclusion> Hyperglycemia-induced microglial proliferation may be associated with tau hyperphosphorylation level. Regional difference of microglial proliferation may underlie the behavioral abnormality caused by hyperglycemia.