Shengyutang Improves Learning and Memory Ability of Sleep Deprived Mice by Regulating Levels of Monoamine Neurotransmitters in Hippocampus / 中国实验方剂学杂志

ABSTRACT

Objective:To observe the effect of Shengyutang on the levels of monoamine neurotransmitters in the hippocampus， and explore its possible mechanism on improving the learning and memory abilities of sleep deprivation （SD） mice. Method:The 50 mice were divided into normal group， model group， estazolam group， Shengyutang low and high dose groups， with 10 mice in each group. A multi-platform water environment was used to prepare SD mouse models. The low and high-dose Shengyutang groups received intragastric administration of 12.5， 25 g·kg^-1， respectively. The mice in the model group were intragastrically administered with the same dose of normal saline daily for 8 weeks. Morris water maze experiment was used to observe the behavioral changes of SD mice in the evasion latency period， the number of crossing platforms， and the stay time in the target quadrant of each group. HE staining was used to observe the pathomorphological changes of the hippocampal tissue of each group. The expression levels of eight monoamine neurotransmitters including serotonin （5-HT），dopandne （DA），epinephrine （EP），norepinephrine （NE），5-hydroxyindole acetic acid（5-HIAA）， high vanillic acid （HVA）， levodopa（<italic>L</italic>-DOPA），and 3，4-dihydroxyphenylacetic acid（DOPAC）were detected by high performance liquid chromatography， and the expression levels of c-Fos protein in hippocampus were detected by immunohistochemistry. Result:Compared with the normal group， the SD mice in the model group were in a poorer general state and severe fatigue was observed. Compared with the model group， SD mice in each dose group of Shengyutang got improved in eating， activity， sleep， hair color， and response to external stimuli. Compared with the normal group， the body weight of SD mice in the model group was significantly reduced （<italic>P</italic><0.05）， but the body weight in the Shengyutang high-dose group increased the most as compared with the model group （<italic>P</italic><0.05）. Compared with the normal group， the hippocampal cells in the model group were disorderly arranged， incomplete in shape， increased in gap and decreased in number. Compared with the model group， the number of neurons in the hippocampus of SD mice in each dose group of Shengyutang increased. Compared with the normal group， the escape latency time of SD mice in the model group was significantly prolonged， the times of crossing platform and the residence time in the target quadrant significantly decreased （<italic>P</italic><0.01）. Compared with the model group， the times of crossing platform and the residence time in the target quadrant of mice in each dose group of Shengyutang significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the normal group， the levels of 5-HT， 5-HIAA， <italic>L</italic>-DOPA， DOPAC， EP， NE， HVA and DA in the model group significantly decreased （<italic>P</italic><0.05，<italic> P</italic><0.01）； but these levels in each dose group of Shengyutang were higher than those in model group （<italic>P</italic><0.05）. Compared with the normal group， the average MD value of c-Fos protein in the hippocampus of the model group significantly increased （<italic>P</italic><0.01）， and the expression levels of c-Fos protein in the hippocampus of Shengyutang groups were significantly lower than those in model group （<italic>P</italic><0.01）. Conclusion:Shengyutang can improve the learning and memory abilities of SD rats， and its mechanism may be related to the decrease of monoamine neurotransmitter and c-Fos protein expression.