阿尔茨海默病三转基因雄性 4 月龄和 8 月龄小鼠模型的焦虑和抑郁样症状研究。
Investigation of Anxiety- and Depressive-like Symptoms in 4- and 8-Month-Old Male Triple Transgenic Mouse Models of Alzheimer's Disease.
机构信息
Center for Neuroscience, Szentágothai Research Center, Institute of Physiology, Medical School, University of Pécs, 7624 Pécs, Hungary.
Laboratory of Behavioral and Stress Studies, Institute of Experimental Medicine, 1083 Budapest, Hungary.
出版信息
Int J Mol Sci. 2022 Sep 16;23(18):10816. doi: 10.3390/ijms231810816.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Approximately 50% of AD patients show anxiety and depressive symptoms, which may contribute to cognitive decline. We aimed to investigate whether the triple-transgenic mouse (3xTg-AD) is a good preclinical model of this co-morbidity. The characteristic histological hallmarks are known to appear around 6-month; thus, 4- and 8-month-old male mice were compared with age-matched controls. A behavioral test battery was used to examine anxiety- (open field (OF), elevated plus maze, light-dark box, novelty suppressed feeding, and social interaction (SI) tests), and depression-like symptoms (forced swim test, tail suspension test, sucrose preference test, splash test, and learned helplessness) as well as the cognitive decline (Morris water maze (MWM) and social discrimination (SD) tests). Acetylcholinesterase histochemistry visualized cholinergic fibers in the cortex. Dexamethasone-test evaluated the glucocorticoid non-suppression. In the MWM, the 3xTg-AD mice found the platform later than controls in the 8-month-old cohort. The SD abilities of the 3xTg-AD mice were missing at both ages. In OF, both age groups of 3xTg-AD mice moved significantly less than the controls. During SI, 8-month-old 3xTg-AD animals spent less time with friendly social behavior than the controls. In the splash test, 3xTg-AD mice groomed themselves significantly less than controls of both ages. Cortical fiber density was lower in 8-month-old 3xTg-AD mice compared to the control. Dexamethasone non-suppression was detectable in the 4-month-old group. All in all, some anxiety- and depressive-like symptoms were present in 3xTg-AD mice. Although this strain was not generally more anxious or depressed, some aspects of comorbidity might be studied in selected tests, which may help to develop new possible treatments.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,也是最常见的痴呆症形式。约 50%的 AD 患者表现出焦虑和抑郁症状,这可能导致认知能力下降。我们旨在研究三重转基因小鼠(3xTg-AD)是否是这种共病的良好临床前模型。已知特征性组织学标志物出现在 6 个月左右;因此,我们比较了 4 月龄和 8 月龄雄性小鼠与年龄匹配的对照组。使用行为测试组合来检查焦虑症(旷场(OF)、高架十字迷宫、明暗箱、新异抑制喂养和社会互动(SI)测试)和抑郁症(强迫游泳测试、悬尾测试、蔗糖偏好测试、飞溅测试和习得性无助)以及认知能力下降( Morris 水迷宫(MWM)和社会辨别(SD)测试)。乙酰胆碱酯酶组织化学可视化了皮质中的胆碱能纤维。地塞米松测试评估了糖皮质激素的不抑制。在 MWM 中,3xTg-AD 小鼠在 8 月龄组中比对照组找到平台的时间晚。3xTg-AD 小鼠在两个年龄组中的 SD 能力均缺失。在 OF 中,两个年龄组的 3xTg-AD 小鼠的移动量明显少于对照组。在 SI 中,8 月龄的 3xTg-AD 动物的友好社交行为时间明显少于对照组。在飞溅测试中,3xTg-AD 小鼠的自我梳理次数明显少于两个年龄段的对照组。与对照组相比,8 月龄 3xTg-AD 小鼠的皮质纤维密度较低。4 月龄组可检测到地塞米松不抑制。总而言之,3xTg-AD 小鼠存在一些焦虑和抑郁样症状。虽然该品系一般不会更焦虑或抑郁,但某些共病方面可能在某些特定测试中进行研究,这可能有助于开发新的潜在治疗方法。