Department of Psychology, Program in Neuroscience, Florida State University, Tallahassee, Florida, USA.
Neurobiology and Behavior, University of California Irvine, Irvine, California, USA.
Sci Rep. 2019 Feb 4;9(1):1311. doi: 10.1038/s41598-018-37151-z.
In early Alzheimer's disease (AD) spatial navigation is impaired; however, the precise cause of this impairment is unclear. Recent evidence suggests that getting lost is one of the first impairments to emerge in AD. It is possible that getting lost represents a failure to use distal cues to get oriented in space. Therefore, we set out to look for impaired use of distal cues for spatial orientation in a mouse model of amyloidosis (3xTg-AD). To do this, we trained mice to shuttle to the end of a track and back to an enclosed start box to receive a water reward. Then, mice were trained to stop in an unmarked reward zone to receive a brain stimulation reward. The time required to remain in the zone for a reward was increased across training, and the track was positioned in a random start location for each trial. We found that 6-month female, but not 3-month female, 6-month male, or 12-month male, 3xTg-AD mice were impaired. 6-month male and female mice had only intracellular pathology and male mice had less pathology, particularly in the dorsal hippocampus. Thus, AD may cause spatial disorientation as a result of impaired use of landmarks.
在早期阿尔茨海默病（AD）中，空间导航会受到损害；然而，这种损害的确切原因尚不清楚。最近的证据表明，迷路是 AD 最早出现的损害之一。迷路可能代表着无法使用远距离线索来确定空间方位。因此，我们着手研究淀粉样蛋白病变（3xTg-AD）小鼠模型中空间定向使用远距离线索受损的情况。为此，我们训练小鼠穿梭到轨道的尽头并返回封闭的起始箱，以获得水奖励。然后，训练小鼠在未标记的奖励区停留以获得脑刺激奖励。随着训练的进行，获得奖励所需的时间会增加，并且每次试验都会随机定位轨道的起始位置。我们发现，6 月龄雌性，但不是 3 月龄雌性、6 月龄雄性或 12 月龄雄性 3xTg-AD 小鼠受损。6 月龄雄性和雌性小鼠只有细胞内病理学，而雄性小鼠的病理学较少，特别是在背侧海马体。因此，AD 可能导致空间定向障碍，原因是无法使用地标。
