Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, United States.
Behav Brain Res. 2012 Oct 1;234(2):259-66. doi: 10.1016/j.bbr.2012.06.014. Epub 2012 Jun 23.
Microvascular disease is defined by microvascular events including arterial wall thickening, microvascular lesions, and microembolic stroke. Characteristics of microvascular disease are observed in the vast majority of patients presenting with late-life depression, and changes in affective behavior may precede microvascular-associated changes in cognitive decline. The current study used a microsphere injection model to test the hypothesis that microembolism infarcts induce depressive-like behaviors in rodents. Further, the study sought to determine whether microembolism-induced changes in affective-like behavior preceded deficits in spatial memory. Microbeads were injected into the internal carotid artery to generate microembolic lesions and behavior was assessed at either a short recovery (SR) time point (4-6 days post-surgery) or long recovery (LR) time point (14-17 days post-surgery). A separate cohort of rats was used to assess spatial memory in the Barnes Maze at the LR time point and beyond (35 days post-surgery). Microembolism infarcts led to an increase in anxiety- and depressive-like behaviors at the LR, but not the SR, time point as evidenced by reduced time in the center of the open field, reduced consumption of a sucrose solution, increased latency to approach a novel female at 14 days and impaired spatial memory at 33 days. A thorough analysis of histological markers and lesion volume revealed that gross histological damage was not predictive of behavioral outcomes, suggesting that alterations in neuronal function may underlie behavioral deficits. Collectively, these data demonstrate that microembolism infarcts are sufficient to induce changes in affective-like behavior and these changes precede alterations in spatial memory.
微血管疾病是由微血管事件定义的，包括动脉壁增厚、微血管病变和微栓塞性中风。在大多数出现老年期抑郁症的患者中观察到微血管疾病的特征，并且情感行为的变化可能先于认知下降与微血管相关的变化。本研究使用微球注射模型来检验这样一个假设，即微栓塞梗死在啮齿动物中引起抑郁样行为。此外，该研究旨在确定情感样行为的微栓塞诱导变化是否先于空间记忆缺陷。微珠被注射到颈内动脉以产生微栓塞病变，并且在短恢复（SR）时间点（手术后 4-6 天）或长恢复（LR）时间点（手术后 14-17 天）评估行为。另一组大鼠用于在 LR 时间点及以后（手术后 35 天）评估 Barnes 迷宫中的空间记忆。微栓塞梗死导致 LR 时间点而不是 SR 时间点的焦虑和抑郁样行为增加，这表现为在开放场的中心停留时间减少，蔗糖溶液消耗减少，在第 14 天接近新雌性的潜伏期增加，以及在第 33 天空间记忆受损。对组织学标志物和病变体积的彻底分析表明，大体组织学损伤不能预测行为结果，这表明神经元功能的改变可能是行为缺陷的基础。总的来说，这些数据表明，微栓塞梗死足以引起情感样行为的变化，并且这些变化先于空间记忆的改变。
