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脆性X综合征小鼠模型:对应激源的行为和激素反应

Mouse model of fragile X syndrome: behavioral and hormonal response to stressors.

作者信息

Nielsen Darci M, Evans Jeffrey J, Derber William J, Johnston Kenzie A, Laudenslager Mark L, Crnic Linda S, Maclean Kenneth N

机构信息

Department of Pediatrics, University of Colorado Denver Medical School, Aurora, CO 80045, USA.

出版信息

Behav Neurosci. 2009 Jun;123(3):677-86. doi: 10.1037/a0015242.

Abstract

Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental retardation protein (FMRP), is characterized by extreme sensitivity to sensory stimuli and increased behavioral and hormonal reactivity to stressors. Fmr1 knockout mice lack FMRP and exhibit abnormal responses to auditory stimuli. This study sought to determine whether Fmr1 knockout mice on an F1 hybrid background are normal in their response to footshock. Knockout mice were also examined for signs of hyperexcitation across an extended trial range, and serum corticosterone levels were evaluated in response to various stressors. The ability to acquire conditioned taste aversion was also assessed. Knockout mice exhibited no impairment in associative aversive learning or memory, since they successfully expressed conditioned taste aversion. Footshock-sensitivity, freezing behavior, and corticosterone response to various stressors did not differ between knockout and wild-type mice. However, knockout mice exhibited significantly increased responses during the extended test. The knockout mice's increased responsiveness to footshock in the extended test may be an indication of increased vulnerability to stress or enhanced emotional reactivity.

摘要

脆性X综合征是一种由脆性X智力低下蛋白(FMRP)水平不足引起的智力迟钝,其特征是对感觉刺激极度敏感,对压力源的行为和激素反应增强。Fmr1基因敲除小鼠缺乏FMRP,对听觉刺激表现出异常反应。本研究旨在确定F1杂交背景下的Fmr1基因敲除小鼠对足部电击的反应是否正常。还检查了基因敲除小鼠在延长试验范围内的过度兴奋迹象,并评估了其对各种压力源的血清皮质酮水平。还评估了获得条件性味觉厌恶的能力。基因敲除小鼠在联想性厌恶学习或记忆方面没有受损,因为它们成功地表现出了条件性味觉厌恶。基因敲除小鼠和野生型小鼠在足部电击敏感性、僵住行为以及对各种压力源的皮质酮反应方面没有差异。然而,在延长试验中,基因敲除小鼠的反应显著增加。基因敲除小鼠在延长试验中对足部电击反应性增加可能表明其对压力的易感性增加或情绪反应增强。

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