谷氨酸单钠透过胎盘屏障对仔鼠特定脑区的结构和功能的影响

TRANSPLACENTAL NEUROTOXIC EFFECtS OF MONOSODIUM GLUTAMATE ON STRUCTURES AND FUNCTIONS OF SPECIFIC BRAIN AREAS OF FILIAL MICE

３－Ｇｌｕ示踪实验表明，谷氨酸可以透过胎盘屏障进入胎鼠体内，较均一地分布于中枢神经系统及内脏各器官。给母鼠隔日注射高、低剂量的谷氨酸单钠（ＭＳＧ，２．５ｍｓ／ｇ，１．０ｍｇ／ｇ）至分娩，对成年后的仔鼠进行检测发现，高剂量组仔鼠记忆能力及Ｙ－迷宫空间分辨学习能力均严重受损，下丘脑弓状核及腹内侧核神经元被明显破坏，出现胞质肿胀、核固缩、神经元数目减少。孕期ＭＳＧ处理还可以使仔鼠下丘脑和海马３Ｈ－Ｇｌｕ受体－配体结合量显著变化。采用ＡＲ－ＣＭ－ＭＩＣ阳离子检测系统观察单个神经元内游离Ｃａ２＋浓度（［Ｃａ２＋］ｉ）的变化时还发现，ＭＳＧ可以通过诱发胞外Ｃａ２＋内流及胞内钙库释放Ｃａ２＋来增高［Ｃａ２＋］ｉ。以上结果提示：ＭＳＧ对仔鼠的剂量依赖性神经毒性作用可能与其过度激活膜谷氨酸受体，引起细胞内Ｃａ２＋超载，最终导致特定脑区的神经元发生溃变甚至死亡有关，而这些变化可能正是仔鼠成年后学习记忆受损的原因。

Monosodium glutumate(MSG) was shown to penetrate placental barrier and distribute almost evenly among embryonic tissues using 3H-Gln as a tracer. When a lower(1. 0 mg/g) and a higher(2. 5 mg/g) doses of MSG were alternatively injected to Kunming maternal mice in every other days from mating to deliveries, obvious injury Occured in the ability of memory retention and y-maze discrimination learning of adult filial mice pregnantly treated with higher doses(2. 5 mg/g) of MSG. Meanwhile, the neuronal damages were observed in not only arcuate nucleus but also ventromedial nucleus of hypothalamus. Characteristic cytopathalogical changes induced by MSG showed swollon cytoplasm, dark pyknotic nuclei and loss of neurons. The radioligandbindings in both hippocampus and hypothalamus altered significantly after the pregnant treatment of MSG. Possible mechanisms underlying MSG excitotoxic phenomena studied in single neuron by use of Ca2+ sensitive indicator Fura-2 with Spex AR-CM-MIC Canon Measurement System, might be dur to increases of intracellular free Ca2+ concentration induced by MSG exposure, which was related to both the influx of Ca2+ and the depletion of Ca2+ from the intracellular Ca2+ stores. These experimental findings in dicated that MSG performed its transplacental neurotoxicity in a dose-dependent manner. The excessive activation of Gin receptors and the overloading of intracellular Ca2+ induced by MSG ultimately leading to neuronal death may result in the reduction of the capability of learning and memory in adult filial mice pregnantly treated with MSG.