BTBR T+tf/J mice: autism-relevant behaviors and reduced fractone-associated heparan sulfate.
BTBR T+tf/J mice: autism-relevant behaviors and reduced fractone-associated heparan sulfate.
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DOI：
10.1016/j.neubiorev.2011.06.008
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发表时间：
2012-01
影响因子：
8.2
通讯作者：
Blanchard, Robert J.
中科院分区：
文献类型：
--
作者：
Blanchard, D. Caroline;Defensor, Erwin B.;Meyza, Ksenia Z.;Pobbe, Roger L. H.;Pearson, Brandon L.;Bolivar, Valerie J.;Blanchard, Robert J.
关键词：
BTBR T+tf/J (BTBR) 小鼠已成为一系列自闭症相关行为模型的有力候选者，显示出社交行为方面的缺陷；在特定情况下超声波发声减少或异常；以及增强的、重复的自我修饰。最近的研究描述了它们在半自然可见洞穴系统（VBS）中的行为；社交接近度测试，其中不可能避免同种人；在对象接近和调查测试中，按照接近/调查对象的顺序评估对特定对象的注意力和潜在的刻板印象。 VBS 结果证实了 BTBR 对同种人的强烈回避，并且在社交接近测试中，BTBR 在几种近距离行为上表现出显着差异，包括对可能与回避凝视有关的鼻对鼻接触的特定回避。地西泮使 BTBR 在三室测试中的社交回避正常化，并在社交接近测试中使一些其他行为（但不是鼻子对鼻子的回避）正常化。 BTBR 还表现出对特定对象的更高水平的偏好，以及以相同顺序调查 3 个或 4 个对象的更高水平的序列。 BTBR 中与侧脑室室下区分形结构相关的硫酸乙酰肝素 (HS) 严重减少。 HS 可能在发育过程中调节一系列生长和引导因子的功能，并且 HS 异常与相关的大脑（胼胝体发育不全）和行为（社交性降低）变化有关；表明在自闭症背景下检查 HS 系统动态的价值。
BTBR T+tf/J (BTBR) mice have emerged as strong candidates to serve as models of a range of autism-relevant behaviors, showing deficiencies in social behaviors; reduced or unusual ultrasonic vocalizations in conspecific situations; and enhanced, repetitive self grooming. Recent studies have described their behaviors in a seminatural Visible Burrow System (VBS); a social proximity test in which avoidance of a conspecific is impossible; and in an object approach and investigation test evaluating attention to specific objects and potential stereotypies in the order of approaching/investigating objects. VBS results confirmed strong BTBR avoidance of conspecifics and in the social proximity test, BTBR showed dramatic differences in several close-in behaviors, including specific avoidance of a nose-to-nose contact that may potentially be related to gaze-avoidance. Diazepam normalized social avoidance by BTBRs in a three-chamber test, and some additional behaviors –but not nose to nose avoidance- in the social proximity test. BTBR also showed higher levels of preference for particular objects, and higher levels of sequences investigating 3- or 4- objects in the same order. Heparan sulfate (HS) associated with fractal structures in the subventricular zone of the lateral ventricles was severely reduced in BTBR. HS may modulate the functions of a range of growth and guidance factors during development, and HS abnormalities are associated with relevant brain (callosal agenesis) and behavioral (reductions in sociality) changes; suggesting the value of examination of the dynamics of the HS system in the context of autism.
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