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Age-dependent impairment of functional hyperemia is associated with amyloid accumulation in small arteries and arterioles in APP transgenic mouse somatosensory cortex
https://repo.qst.go.jp/records/70448
https://repo.qst.go.jp/records/70448504a2850-9835-498d-b857-c48b3300b32c
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-06-01 | |||||
| タイトル | ||||||
| タイトル | Age-dependent impairment of functional hyperemia is associated with amyloid accumulation in small arteries and arterioles in APP transgenic mouse somatosensory cortex | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Takuwa, Hiroyuki
× Takuwa, Hiroyuki× et.al× 田桑 弘之 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: In order to explore the causal relationship between cerebrovascular dysfunction and pathogenesis of Alzheimer's disease, we performed a repeated longitudinal evaluation of CBF response to whisker stimulation and accumulation of amyloid in APP transgenic mouse somatosensory cortex. Methods: Long-term evaluation of CBF response and behavior activity was performed (Takuwa et al., 2010), every 2 to 4 weeks with laser-Doppler flowmetry (LDF) and an optical motion sensor, respectively in awake APP transgenic mice (3-27 months). Whisker stimulation was performed to provoke CBF response. On a separate date, amyloid and microvessels were fluorescently labeled with a compound X (newly-developed by our group) and sulforhodamine 101, respectively, and two-photon imaging (1024 by 1024 pixels) was performed with a z-step size of 4 µm (Fig. 1). Accumulation of vascular amyloid and tissue amyloid were evaluated separately. The thickness of the vascular amyloid was evaluated at several point along a particular vessel as the difference between the outer diameter of the vessel wall and the outer diameter of the amyloid. The fraction of the vessel covered by vascular amyloid was evaluated by measuring the length of non-amyloid spaces. The tissue amyloid was evaluated by calculating the area covered by labeled amyloid in the parechymal tissue. Results: We observed that evoked CBF age-dependently declined with age from 3 months (23%) to 27 months (5.5%), while animal locomotion and heart rate were preserved. Further detailed analysis suggested that the age-dependent decline of cerebrovascular functions increased dramatically after about 17 months (6.8% at minimum). On the other hand, the accumulation of amyloid was found to be detectable in the parenchyma tissue and the vessel wall of small arteries at 14 months. The accumulation of the tissue amyloid gradually increased and the vascular amyloid expanded from the arteries to arterioles between the ages from 14 to 19 months. The thickness of the vascular amyloid at 19 months was 60% higher than that at 14 months. The length of non-vascular-amyloid spaces at 19 months decreased to 82% of that at 14 months. The size of the tissue amyloid at 19 months increased by 70% relative to that at 14 months. Discussion: The results indicate that the impairment of CBF response is caused by i) age-dependent decline of the proteolytic activity and/or clearance of the parenchymal amyloid, and/or ii) direct toxic effects of the cerebral amyloid angiopathy at small arteries and arterioles on the cerebrovascular function. Reference: Takuwa H, Autio J, Nakayama H, Matsuura T, Obata T, Okada E, Masamoto K, Kanno I. (2010) Reproducibility and Variance of a Stimulation-Induced Hemodynamic Response in Barrel Cortex of Awake Behaving Mice. Brain Res. In press |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Brain 2011 | |||||
| 発表年月日 | ||||||
| 日付 | 2011-05-28 | |||||
| 日付タイプ | Issued | |||||
