Alzheimer's Disease Mutant Mice Exhibit Reduced Brain Tissue Stiffness Compared to Wild-type Mice in both Normoxia and following Intermittent Hypoxia Mimicking Sleep Apnea

与野生型小鼠相比,阿尔茨海默病突变小鼠在常氧和间歇性缺氧(模拟睡眠呼吸暂停)条件下的脑组织硬度均降低

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作者:Maria José Menal, Ignasi Jorba, Marta Torres, Josep M Montserrat, David Gozal, Anna Colell, Gerard Piñol-Ripoll, Daniel Navajas, Isaac Almendros, Ramon Farré

Aim

To investigate whether intermittent hypoxia (IH) alters brain cortex tissue stiffness in AD mutant mice exposed to IH mimicking OSA.

Background

Evidence from patients and animal models suggests that obstructive sleep apnea (OSA) may increase the risk of Alzheimer's disease (AD) and that AD is associated with reduced brain tissue stiffness.

Conclusion

AD mutant mice exhibit reduced brain tissue stiffness following both normoxia and IH mimicking sleep apnea, and such differences are commensurate with increased edema and demyelination in AD.

Methods

Six-eight month old (B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J) AD mutant mice and wild-type (WT) littermates were subjected to IH (21% O2 40 s to 5% O2 20 s; 6 h/day) or normoxia for 8 weeks. After euthanasia, the stiffness (E) of 200-μm brain cortex slices was measured by atomic force microscopy.

Results

Two-way ANOVA indicated significant cortical softening and weight increase in AD mice compared to WT littermates, but no significant effects of IH on cortical stiffness and weight were detected. In addition, reduced myelin was apparent in AD (vs. WT), but no significant differences emerged in the cortex extracellular matrix components laminin and glycosaminoglycans when comparing baseline AD and WT mice.

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