Department of Biology, Colby College, 5550 Mayflower Hill Dr., Waterville, ME 04901, USA.
Department of Psychology, Colby College, 5550 Mayflower Hill Dr., Waterville, ME 04901, USA.
Neuroscience. 2017 Oct 11;361:116-128. doi: 10.1016/j.neuroscience.2017.07.071. Epub 2017 Aug 5.
Choline is essential to the development and function of the central nervous system and supplemental choline during development is neuroprotective against a variety of insults, including neurotoxins like dizocilpine (MK-801). MK-801 is an NMDA receptor antagonist that is frequently used in rodent models of psychological disorders, particularly schizophrenia. At low doses, it causes cognitive impairments, and at higher doses it induces motor deficits, anhedonia, and neuronal degeneration. The primary goals of the present study were to investigate whether prenatal choline supplementation protects against the cognitive impairments, motor deficits, and neuropathologies that are precipitated by MK-801 administration in adulthood. Adult male Sprague-Dawley rats were fed a standard or supplemented choline diet prenatally. Using the novelty preference test of object recognition, we found that only prenatal standard-fed rats displayed memory consolidation deficits induced by low-dose MK-801 administered immediately following study of sample objects; all other groups, including prenatal choline supplemented rats given MK-801, showed intact memory. Following high-dose MK-801, prenatal choline supplementation significantly alleviated rats' motor response to MK-801, particularly ataxia. Using doublecortin and Ki67 to mark neurogenesis and cell division, respectively, in the hippocampus, we found that prenatal choline supplementation, in the face of MK-801 toxicity, protected against reduced hippocampal plasticity. Taken together, the current findings suggest that prenatal choline supplementation protects against a variety of behavioral and neural pathologies induced by the neurotoxin, MK-801. This research contributes to the growing body of evidence supporting the robust neuroprotective capacity of choline.
胆碱对中枢神经系统的发育和功能至关重要，在发育过程中补充胆碱可预防多种损伤，包括神经毒素如地卓西平（MK-801）。MK-801 是一种 NMDA 受体拮抗剂，常用于心理障碍的啮齿动物模型，特别是精神分裂症。低剂量时，它会导致认知障碍，高剂量时会引起运动缺陷、快感缺失和神经元变性。本研究的主要目的是研究产前胆碱补充是否可以预防 MK-801 在成年期给药引起的认知障碍、运动缺陷和神经病理学。成年雄性 Sprague-Dawley 大鼠在产前接受标准或补充胆碱饮食。使用物体识别的新颖性偏好测试，我们发现只有产前标准喂养的大鼠在学习样本物体后立即给予低剂量 MK-801 时显示出记忆巩固缺陷；所有其他组，包括产前给予 MK-801 的胆碱补充大鼠，都显示出完整的记忆。在高剂量 MK-801 后，产前胆碱补充显著缓解了大鼠对 MK-801 的运动反应，特别是共济失调。使用双皮质素和 Ki67 分别标记海马中的神经发生和细胞分裂，我们发现，面对 MK-801 的毒性，产前胆碱补充可防止海马可塑性降低。综上所述，目前的研究结果表明，产前胆碱补充可预防神经毒素 MK-801 引起的多种行为和神经病理学变化。这项研究为支持胆碱强大的神经保护能力的不断增加的证据做出了贡献。
