Microembolism infarcts lead to delayed changes in affective-like behaviors followed by spatial memory impairment

被引:28
作者
Nemeth, Christina L. [1 ,3 ]
Shurte, Mallory S. [1 ]
McTigue, Dana M. [4 ]
Nemeroff, Charles B. [5 ]
Neigh, Gretchen N. [1 ,2 ,3 ]
机构
[1] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA
[2] Ctr Behav Neurosci, Atlanta, GA USA
[3] Emory Univ, Dept Physiol, Atlanta, GA 30322 USA
[4] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA
[5] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA
关键词
Microembolism; Microvascular; Spatial memory; Anhedonia; Anxiety; Depression; SILENT BRAIN INFARCTS; SMALL-VESSEL DISEASE; MICROSPHERE EMBOLISM; CEREBRAL INFARCTION; CARDIAC-ARREST; STROKE; DEPRESSION; STRESS;
D O I
10.1016/j.bbr.2012.06.014
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
010107 [宗教学]; 030301 [社会学]; 070906 [古生物学及地层学(含古人类学)];
摘要
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. (C) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:259 / 266
页数:8
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