Nishigaki Ruriko, Yokoyama Yoshihiro, Shimizu Yuko, Marumoto Ryosuke, Misumi Sachiyo, Ueda Yoshitomo, Ishida Akimasa, Shibuya Yasuyuki, Hida Hideki
Department of Neurophysiology & Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Department of Neurophysiology & Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan; Department of Neurophysiology and Oral Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Brain Res. 2018 Jul 1;1690:40-50. doi: 10.1016/j.brainres.2018.04.006. Epub 2018 Apr 9.
We used an umami substance, monosodium glutamate (MSG), as a simple stimulant to clarify the mechanism of the formation of emotional behavior. A 60 mM MSG solution was fed to spontaneously hypertensive rats (SHR), used as a model of attention-deficit hyperactivity disorder, from postnatal day 25 for 5 weeks kept in isolation. Emotional behaviors (anxiety and aggression) were then assessed by the open-field test, cylinder test and social interaction test. MSG ingestion during the developmental period resulted in a significant reduction in aggressive behavior but had few effects on anxiety-like behavior. Several experiments were performed to identify the reason for the reduced aggression with MSG intake. Blood pressure in the MSG-treated SHR was comparable to that of the controls during development. Argyrophil III staining to detect the very early phase of neuronal damage revealed no evidence of injury by MSG in aggression-related brain areas. Assessment of plasma amino acids revealed that glutamate levels remained constant (∼80 μM) with MSG ingestion, except for a transient increase after fasting (∼700 μM). However, lactate dehydrogenase assay in an in vitro blood-brain barrier model showed that cell toxicity was not induced by indirect MSG application even at 700 μM, confirming that MSG ingestion caused minimal neuronal damage. Finally, vagotomy at the sub-diaphragmatic level before MSG ingestion blocked its effect on aggressive behavior in the isolated SHR. The data suggest that MSG ingestion during the developmental period can reduce aggressive behavior in an attention deficit-hyperactivity disorder model rat, mediated by gut-brain interaction.
我们使用鲜味物质谷氨酸钠（MSG）作为一种简单的刺激物，以阐明情绪行为形成的机制。从出生后第25天开始，将60 mM的MSG溶液喂给作为注意力缺陷多动障碍模型的自发性高血压大鼠（SHR），持续5周，并将其单独饲养。然后通过旷场试验、圆筒试验和社交互动试验评估情绪行为（焦虑和攻击性）。发育期间摄入MSG导致攻击性行为显著减少，但对焦虑样行为影响不大。进行了多项实验以确定摄入MSG后攻击性行为减少的原因。在发育过程中，接受MSG处理的SHR的血压与对照组相当。用于检测神经元损伤早期阶段的嗜银III染色显示，在与攻击行为相关的脑区没有MSG损伤的证据。血浆氨基酸评估显示，摄入MSG后谷氨酸水平保持恒定（约80μM），除了禁食后短暂升高（约700μM）。然而，在体外血脑屏障模型中进行的乳酸脱氢酶测定表明，即使在700μM时，间接应用MSG也不会诱导细胞毒性，这证实摄入MSG引起的神经元损伤最小。最后，在摄入MSG之前在膈下水平进行迷走神经切断术，阻断了其对隔离饲养的SHR攻击性行为的影响。数据表明，发育期间摄入MSG可以减少注意力缺陷多动障碍模型大鼠的攻击性行为，这是由肠-脑相互作用介导的。
