Department of Psychology, Colby College, Waterville, ME 04901, USA.
Pharmacol Biochem Behav. 2012 Nov;103(1):60-8. doi: 10.1016/j.pbb.2012.08.002.
In the present study, we investigated whether the essential nutrient choline may protect against schizophrenic-like cognitive deficits in a rat model. Theories regarding the etiology of schizophrenia suggest that early life events render an individual more vulnerable to adult challenges, and the combination may precipitate disease onset. To model this, the adult male offspring of dams who either experienced stress during late gestation or did not were given a 5 mg/kg dose of the NMDA antagonist,MK-801. The presence of both the prenatal challenge of stress and the adult challenge of MK-801 was expected to impair memory in these offspring. Memory was not expected to be impaired in rats that did not experience prenatal stress, but did receive MK-801 as adults. To study whether choline levels altered outcomes in these groups, rats were fed a choline-supplemented, -deficient, or standard diet during the period between the two challenges: beginning at weaning and continuing for 25 days. All rats consumed regular rat chow thereafter. The efficacy of the model was confirmed in the standard fed rats in that only those that were prenatally stressed and received MK-801 as adults displayed impaired memory on a novelty preference test of object recognition. Contrary to this finding and consistent with our hypothesis, choline-supplemented rats that were also both prenatally stressed and given MK-801 as adults showed intact memory. Choline deficiency impaired memory in rats that were just prenatally stressed, just given MK-801 as adults, and subjected to both. Thus, a choline deficient diet may render rats vulnerable to either challenge. Taken together, we offer evidence that developmental choline levels modulate the effects of prenatal stress and/or MK-801 and thereby alter the cognitive outcome in a rat model of schizophrenia.
在本研究中，我们研究了必需营养素胆碱是否可以预防精神分裂症样认知缺陷的发生。关于精神分裂症病因的理论表明，早期生活事件使个体更容易受到成年期挑战的影响，而两者的结合可能会引发疾病的发生。为了模拟这种情况，接受过孕晚期应激的母鼠的雄性成年后代或未接受过应激的母鼠的雄性成年后代接受了 5mg/kg 的 NMDA 拮抗剂 MK-801。预计母体应激的产前挑战和成年期的 MK-801 挑战都会损害这些后代的记忆。未经历过产前应激但成年后接受 MK-801 的大鼠的记忆预计不会受损。为了研究胆碱水平是否改变了这些组的结果，大鼠在两次挑战之间（从断奶开始并持续 25 天）接受了补充胆碱、缺乏胆碱或标准饮食。此后，所有大鼠均食用常规大鼠饲料。在标准喂养的大鼠中，该模型的功效得到了证实，只有那些经历过产前应激并在成年期接受 MK-801 的大鼠在物体识别新颖偏好测试中表现出记忆受损。与这一发现相反，与我们的假设一致，同时经历产前应激和成年期给予 MK-801 的补充胆碱的大鼠表现出完整的记忆。胆碱缺乏症会损害仅经历产前应激、仅接受成年期给予的 MK-801 以及同时经历两者的大鼠的记忆。因此，胆碱缺乏饮食可能使大鼠易受任何一种挑战的影响。综上所述，我们提供的证据表明，发育中的胆碱水平调节产前应激和/或 MK-801 的影响，并由此改变精神分裂症大鼠模型的认知结果。
