演題詳細
Oral
アルツハイマー病、他の認知症、老化 3
Alzheimer's Disease, Other Dementia, Aging 3
| 開催日 | 2014/9/12 |
|---|---|
| 時間 | 15:00 - 16:00 |
| 会場 | Room I（311+312） |
| Chairperson(s) | 玉岡 晃 / Akira Tamaoka (筑波大学医学医療系神経内科学 / Department of Neurology, University of Tsukuba, Japan) 田口 明子 / Akiko Taguchi (宮崎大学医学部神経呼吸内分泌代謝学分野 / Department of Neurology, Respirology, Endocrinology and Metabolism, Miyazaki University School of Medicine, Japan) |
神経系IRS2の欠損は加齢関連の認知機能低下を抑制する
Neural IRS2 deficiency prevents age-related cognitive decline
- O2-I-3-4
- 田口 明子 / Akiko Taguchi:1,2 牧ノ段 学 / Manabu Makinodan:3,4 岸本 年史 / Toshifumi Kishimoto:4 ガブリエル コファス / Gabriel Corfas:3 ホワイト モーリス / Morris White:2
- 1:宮崎大学 / Division of Neurology, Respirology, Endocrinology, and Metabolism, Department of Internal Medicine, University of Miyazaki, Japan 2:Div Endocrinology,Childrens Hospital Boston Harvard Med Sch, Boston, MA , USA / Div Endocrinology,Childrens Hospital Boston Harvard Med Sch, Boston, MA , USA 3:Dept Neurology and Otolaryngology ,Childrens Hospital Boston Harvard Med Sch, Boston, MA , USA / Dept Neurology and Otolaryngology ,Childrens Hospital Boston Harvard Med Sch, Boston, MA , USA 4:奈良医大医精神医学 / Dept Psychiatry, Nara Medical University, Japan
Diabetes mellitus (DM) that impairs cognitive function and adult hippocampal neurogenesis is a risk factor for Alzheimer's disease (AD) as with aging. Previous studies show that less neural IRS2 (Insulin Receptor Substrates2) increases lifespan and reverses premature mortality with reducing aggregated Aβ in AD model mice, while displaying hyperinsulinemia that is considered to be a pre-DM condition. Here we show that IRS2 is expressed in both mature neurons and neural stem/progenitor cells in the hippocampal dentate gyrus (DG). Cell proliferation and neuronal differentiation remarkably augmented in aged mice lacking neural IRS2 (BIRS2ko). In the process of neuronal differentiation, neural IRS2 depletion increased dendritic complexity and decreased microglial activation in the DG of aged mice. Moreover, the Water T-maze protocol demonstrated that the test accuracy ratios in aged BIRS2ko mice were significantly greater than those in age-matched controls. Thus, less neural IRS2 signaling facilitates adult neurogenesis and inhibits cognitive decline in aged mice regardless of hyperinsulinemia.