Mao Chun-ting, Li Ting-yu, Liu You-xue, Qu Ping
Department of Child Health Care, Children's Hospital, Chongqing Medical University, Chongqing 400014, China.
Zhonghua Er Ke Za Zhi. 2005 Jul;43(7):526-30.
Previous studies have demonstrated that vitamin A and its active derivatives function as essential competence factors for long-term synaptic plasticity within the adult brain. But little is known if marginal vitamin A deficiency (MVAD) beginning from embryonic period affects the brain development and the ability of learning and memory in young rats. The aim of this study was to identify the effects of MVAD and vitamin A intervention (VAI) on learning, memory and the hippocampal CA1 long-term potentiation (LTP) in young rats.
Rats were divided into control, MVAD and VAI groups in this study. In control group (10 young rats) the dams and pups were fed with normal diet (VA 6500 IU/kg). In MVAD group (19 young rats) the dams and pups were fed with MVAD diet (VA 400 IU/kg). In VAI group (9 young rats) the dams were fed with MVAD diet and the pups were fed with normal diet from postnatal week 4. All the young rats were killed at the age of 7 weeks. During the last week of the experiment, the shuttle box active avoidance reaction tests were carried out. At week 7, the hippocampal CA1 LTP was detected by electrophysiological technique and relative intensity of fluorescence in cells in hippocampal slices was measured by confocal laser scanning microscopy labeled by fluo-3.
(1) The times to reach the learning standard in both VAI group (28.8 +/- 4.1) and MVAD group (45.6 +/- 12.1) were more than control group (17.1 +/- 4.4) (P < 0.01), and that of MVAD group was more than VAI group (P < 0.05) in active avoidance reaction tests. (2) The changes of field excitatory postsynaptic potentials (fEPSP) slope for MVAD group (22.9% +/- 9.4%) and VAI group (29.5% +/- 13.7%) were less than that of control group (57.5% +/- 27.3%), respectively (P < 0.01). No significant difference was found between VAI and MVAD groups (P > 0.05). (3) No significant differences of relative intensity of fluorescence in cells were found among the three groups before the tetanus stimulation. However, the significantly low relative intensity of fluorescence in cells was seen in MVAD (65.1 +/- 17.0) and VAI (85.8 +/- 17.1) groups compared with control group (113.6 +/- 20.5) after the tetanus stimulation (P < 0.01), and that of VAI group was higher than that of MVAD group (P < 0.05).
MVAD beginning from embryonic period impairs learning, memory and LTP in young rats. But the losses might not be reversible if the vitamin A supplementation is late especially missing the critical period of hippocampus development. According to the experimental data, it is speculated that vitamin A may modulate the influx of calcium ion to influence the LTP and lead to the change of learning and memory.
以往研究表明，维生素A及其活性衍生物是成年大脑中长期突触可塑性的重要关键因素。但从胚胎期开始的边缘性维生素A缺乏（MVAD）是否会影响幼鼠的大脑发育及学习记忆能力，目前尚不清楚。本研究旨在确定MVAD和维生素A干预（VAI）对幼鼠学习、记忆及海马CA1区长期增强（LTP）的影响。
本研究将大鼠分为对照组、MVAD组和VAI组。对照组（10只幼鼠）的母鼠和幼鼠喂食正常饮食（维生素A 6500 IU/kg）。MVAD组（19只幼鼠）的母鼠和幼鼠喂食MVAD饮食（维生素A 400 IU/kg）。VAI组（9只幼鼠）的母鼠喂食MVAD饮食，幼鼠从出生后第4周开始喂食正常饮食。所有幼鼠在7周龄时处死。在实验的最后一周，进行穿梭箱主动回避反应测试。在第7周，采用电生理技术检测海马CA1区LTP，并通过共聚焦激光扫描显微镜用fluo-3标记测量海马切片中细胞的相对荧光强度。
（1）在主动回避反应测试中，VAI组（28.8±4.1）和MVAD组（45.6±12.1）达到学习标准的次数均多于对照组（17.1±4.4）（P<0.01），且MVAD组多于VAI组（P<0.05）。（2）MVAD组（22.9%±9.4%）和VAI组（29.5%±13.7%）的场兴奋性突触后电位（fEPSP）斜率变化分别小于对照组（57.5%±27.3%）（P<0.01）。VAI组和MVAD组之间无显著差异（P>0.05）。（3）在强直刺激前，三组细胞的相对荧光强度无显著差异。然而，强直刺激后，MVAD组（65.1±17.0）和VAI组（85.8±17.1）细胞的相对荧光强度明显低于对照组（113.6±20.5）（P<0.01），且VAI组高于MVAD组（P<0.05）。
从胚胎期开始出现的MVAD会损害幼鼠的学习、记忆和LTP。但如果维生素A补充过晚，尤其是错过海马发育的关键期，这些损害可能无法逆转。根据实验数据推测，维生素A可能通过调节钙离子内流来影响LTP，进而导致学习记忆的改变。
