恐伤孕鼠所产21日龄仔鼠的认知发育与海马区GLU、GABA、GLY的相关性研究
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摘要
目的:考察恐伤孕鼠所产21日龄仔鼠认知发育与海马区谷氨酸(Glutamic acid, GLU)、γ-氨基丁酸(Gamma-aminobutyric acid, GABA)、甘氨酸(Glycine, GLY)的相关性。方法:应用旁观电击法建立恐伤肾孕鼠模型,通过对21日龄仔鼠进行Morris水迷宫实验,观察其认知发育;通过脑立体定位仪在右侧海马区采集脑透析液,应用HPLC-ECD法测定仔鼠脑透析液中GLU、GABA、GLY含量。结果:与对照组比较,21日龄模型组仔鼠平均逃避潜伏期时间久、游泳速度慢、跨台次数少、20%边缘区域停留时间长,差异均有统计学意义(P<0.05);21日龄模型组仔鼠海马组织细胞外液中GLU、GLY的水平在各个灌流时间点均升高,而GABA的水平在各个灌流时间点均降低,差异有统计学意义(P<0.05);21日龄仔鼠海马区氨基酸类神经递质GLU、GLY与其平均逃避潜伏期、跨台次数存在负相关,与20%边缘区域停留时间呈正相关关系,差异有统计学意义(P<0.05);神经递质GABA与其平均逃避潜伏期、跨台次数存在正相关,与20%边缘区域停留时间呈负相关关系,差异有统计学意义(P<0.05)。结论:恐伤孕鼠可影响其21日龄仔鼠的认知发育及海马区GLU、GABA、GLY的含量,其认知发育水平与海马区GLU、GABA、GLY的含量改变有一定的关系。
Objective: To study the correlation between cognitive development and GLU, GABA and GLY in hippocampus of 21-day-old neonatal rats of fear-impaired pregnant rats. Methods: Fear-impaired pregnant rats were established by watching other rats shocked by electricity. Cognitive developments were observed by Morris water maze test on the 21 st day after birth. Brain microdialysis of the right hippocampus was collected with the stereotaxis instrument to determine the levels of GLU, GABA and GLY by HPLC-ECD. Results: Compared with the control group, the average escape latency time was longer, the swimming speed was slower, the times of crossing platform was decreased, the time staying at the 20% edge area of the 21-day-old rats was longer in the model group, and the differences were statistically significant(P<0.05). Levels of GLU and GLY in hippocampus of 21-day-old rats in the model group of cells were increased in different liquid perfusion time points, while GABA was reduced, and the differences were statistically significant(P<0.05). There was a negative correlation between the levels of GLU and GLY in hippocampus of the 21-day-old rats and the average escape latency time, the times of crossing platform, while there was a positive correlation between the levels of GLU, GLY and the time staying at the 20% edge area, and the differences were statistically significant(P<0.05). There was a positive correlation between the level of neurotransmitter GABA and the average escape latency time, the times of crossing platform, while there was a negative correlation between the level of neurotransmitter GABA and the time staying at the 20% edge area, and the differences were statistically significant(P<0.05). Conclusion: Cognitive development and the concentrations of GLU, GABA and GLY in the hippocampus of 21-day-old rats were significantly affected by fear-impaired pregnant rats, and the level of cognitive development was related to the concentrations of GLU, GABA and GLY in hippocampus.
Objective: To study the correlation between cognitive development and GLU, GABA and GLY in hippocampus of 21-day-old neonatal rats of fear-impaired pregnant rats. Methods: Fear-impaired pregnant rats were established by watching other rats shocked by electricity. Cognitive developments were observed by Morris water maze test on the 21 st day after birth. Brain microdialysis of the right hippocampus was collected with the stereotaxis instrument to determine the levels of GLU, GABA and GLY by HPLC-ECD. Results: Compared with the control group, the average escape latency time was longer, the swimming speed was slower, the times of crossing platform was decreased, the time staying at the 20% edge area of the 21-day-old rats was longer in the model group, and the differences were statistically significant(P<0.05). Levels of GLU and GLY in hippocampus of 21-day-old rats in the model group of cells were increased in different liquid perfusion time points, while GABA was reduced, and the differences were statistically significant(P<0.05). There was a negative correlation between the levels of GLU and GLY in hippocampus of the 21-day-old rats and the average escape latency time, the times of crossing platform, while there was a positive correlation between the levels of GLU, GLY and the time staying at the 20% edge area, and the differences were statistically significant(P<0.05). There was a positive correlation between the level of neurotransmitter GABA and the average escape latency time, the times of crossing platform, while there was a negative correlation between the level of neurotransmitter GABA and the time staying at the 20% edge area, and the differences were statistically significant(P<0.05). Conclusion: Cognitive development and the concentrations of GLU, GABA and GLY in the hippocampus of 21-day-old rats were significantly affected by fear-impaired pregnant rats, and the level of cognitive development was related to the concentrations of GLU, GABA and GLY in hippocampus.
引文
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[3] Huang Y, Shen Z, Hu L, et al. Exposure of mother rats to chronic unpredictable stress before pregnancy alters the metabolism of gamma-aminobutyric acid and glutamate in the right hippocampus of offspring in early adolescence in a sexually dimorphic manner[J]. Psychiatry Res, 2016, 246: 236-245.
[4] 杨丽萍, 袁福宁, 李新民, 等. 恐伤母鼠对仔鼠空间学习及记忆能力影响[J]. 中国公共卫生, 2013, 29(2): 214-216.
[5] 李新民, 杨丽萍, 万海娇, 等. 恐伤孕鼠所产80日龄仔鼠情志与海马区去甲肾上腺素和肾上腺素水平的相关性研究[J]. 中国全科医学, 2017, 20(23): 2875-2878.
[6] Cassella SN, Hemmerle AM, Lundgren KH, et al. Maternal immune activation alters glutamic acid decarboxylase-67 expression in the brains of adult rat offspring[J]. Schizophr Res, 2016, 171(1-3):195-199.
[7] Guilarte TR. Regional changes in the concentrations of glutamate, glycine, taurine, and GABA in the vitamin B-6 deficient developing rat brain: association with neonatal seizures[J]. Neurochem Res, 1989, 14(9):889-897.
[8] Zhang Y, Lu W, Han M, et al. Biphasic Effects of Copper on Rat Learning and Memory in the Morris Water Maze[J]. Ann Clin Lab Sci, 2016, 46(4): 346-352.
[9] 唐映红, 王一奇, 周惠芬, 等. 微透析法研究麻黄汤对大鼠脑海马区氨基酸类神经递质释放的影响[J]. 中国药理学通报, 2017, 33(3): 426-432.
[10] 魏凤环, 罗佳波, 莫志贤. 麻黄配伍前后对大鼠大脑额叶皮层氨基酸类神经递质含量的影响[J]. 山东中医药大学学报, 2006, 30(5): 392-394.
[11] 张士善, 张力, 张丹参. 脑内Glu/GABA学习记忆调节系统[J]. 药学学报, 1997, 32(8): 638-640.
[12] Luo J, Min S, Wei K, et al. Propofol protects against impairment of learning-memory and imbalance of hippocampal Glu/GABA induced by electroconvulsive shock in depressed rats[J]. J Anesth, 2011, 25(5):657-665.
[13] Amorini AM, Lazzarino G, Di Pietro V, et al. Severity of experimental traumatic brain injury modulates changes in concentrations of cerebral free amino acids[J]. J Cell Mol Med, 2017, 21(3): 530-542.
[14] Zheng H, Zheng Y, Zhao L, et al. Cognitive decline in type 2 diabetic db/db mice may be associated with brain region-specific metabolic disorders[J]. Biochim Biophys Acta, 2017, 1863(1): 266-273.
[15] Ou CY, Luo YN, He SN, et al. Sodium P-Aminosalicylic Acid Improved Manganese-Induced Learning and Memory Dysfunction via Restoring the Ultrastructural Alterations and γ-Aminobutyric Acid Metabolism Imbalance in the Basal Ganglia[J]. Biol Trace Elem Res, 2017, 176(1):143-153.
[16] Venton BJ, Robinson TE, Kennedy RT. Transient changes in nucleus accumbens amino acid concentrations correlate with individual responsivity to the predator fox odor 2,5-dihydro-2,4,5-trimethylthiazoline[J]. J Neurochem, 2006, 96(1): 236-246.
[17] 游秋云, 王平, 吴丽丽, 等. 舒郁安神方对老年肝郁失眠证候模型大鼠学习记忆及脑组织谷氨酸、γ-氨基丁酸含量的影响[J]. 中国老年学杂志, 2011, 31(6): 1006-1009.
[18] 王杰, 王蔚, 虞献民, 等. 代谢型谷氨酸受体激动剂3,5-二羟基苯甘氨酸对大鼠学习记忆行为的影响[J]. 中国临床神经科学, 2016, 24(4): 371-375.
[19] Locci A, Porcu P, Talani G, et al. Neonatal estradiol exposure to female rats changes GABAA receptor expression and function, and spatial learning during adulthood[J]. Horm Behav, 2016, 87: 35-46.
[20] Li G, Lv J, Wang J, et al. GABAB receptors in the hippocampal dentate gyrus are involved in spatial learning and memory impairment in a rat model of vascular dementia[J]. Brain Res Bull, 2016, 124: 190-197.
[2] Carr F. Learning and memory: conditions for fear[J]. Nat Rev Neurosci, 2015, 16(10): 576-577.
[3] Huang Y, Shen Z, Hu L, et al. Exposure of mother rats to chronic unpredictable stress before pregnancy alters the metabolism of gamma-aminobutyric acid and glutamate in the right hippocampus of offspring in early adolescence in a sexually dimorphic manner[J]. Psychiatry Res, 2016, 246: 236-245.
[4] 杨丽萍, 袁福宁, 李新民, 等. 恐伤母鼠对仔鼠空间学习及记忆能力影响[J]. 中国公共卫生, 2013, 29(2): 214-216.
[5] 李新民, 杨丽萍, 万海娇, 等. 恐伤孕鼠所产80日龄仔鼠情志与海马区去甲肾上腺素和肾上腺素水平的相关性研究[J]. 中国全科医学, 2017, 20(23): 2875-2878.
[6] Cassella SN, Hemmerle AM, Lundgren KH, et al. Maternal immune activation alters glutamic acid decarboxylase-67 expression in the brains of adult rat offspring[J]. Schizophr Res, 2016, 171(1-3):195-199.
[7] Guilarte TR. Regional changes in the concentrations of glutamate, glycine, taurine, and GABA in the vitamin B-6 deficient developing rat brain: association with neonatal seizures[J]. Neurochem Res, 1989, 14(9):889-897.
[8] Zhang Y, Lu W, Han M, et al. Biphasic Effects of Copper on Rat Learning and Memory in the Morris Water Maze[J]. Ann Clin Lab Sci, 2016, 46(4): 346-352.
[9] 唐映红, 王一奇, 周惠芬, 等. 微透析法研究麻黄汤对大鼠脑海马区氨基酸类神经递质释放的影响[J]. 中国药理学通报, 2017, 33(3): 426-432.
[10] 魏凤环, 罗佳波, 莫志贤. 麻黄配伍前后对大鼠大脑额叶皮层氨基酸类神经递质含量的影响[J]. 山东中医药大学学报, 2006, 30(5): 392-394.
[11] 张士善, 张力, 张丹参. 脑内Glu/GABA学习记忆调节系统[J]. 药学学报, 1997, 32(8): 638-640.
[12] Luo J, Min S, Wei K, et al. Propofol protects against impairment of learning-memory and imbalance of hippocampal Glu/GABA induced by electroconvulsive shock in depressed rats[J]. J Anesth, 2011, 25(5):657-665.
[13] Amorini AM, Lazzarino G, Di Pietro V, et al. Severity of experimental traumatic brain injury modulates changes in concentrations of cerebral free amino acids[J]. J Cell Mol Med, 2017, 21(3): 530-542.
[14] Zheng H, Zheng Y, Zhao L, et al. Cognitive decline in type 2 diabetic db/db mice may be associated with brain region-specific metabolic disorders[J]. Biochim Biophys Acta, 2017, 1863(1): 266-273.
[15] Ou CY, Luo YN, He SN, et al. Sodium P-Aminosalicylic Acid Improved Manganese-Induced Learning and Memory Dysfunction via Restoring the Ultrastructural Alterations and γ-Aminobutyric Acid Metabolism Imbalance in the Basal Ganglia[J]. Biol Trace Elem Res, 2017, 176(1):143-153.
[16] Venton BJ, Robinson TE, Kennedy RT. Transient changes in nucleus accumbens amino acid concentrations correlate with individual responsivity to the predator fox odor 2,5-dihydro-2,4,5-trimethylthiazoline[J]. J Neurochem, 2006, 96(1): 236-246.
[17] 游秋云, 王平, 吴丽丽, 等. 舒郁安神方对老年肝郁失眠证候模型大鼠学习记忆及脑组织谷氨酸、γ-氨基丁酸含量的影响[J]. 中国老年学杂志, 2011, 31(6): 1006-1009.
[18] 王杰, 王蔚, 虞献民, 等. 代谢型谷氨酸受体激动剂3,5-二羟基苯甘氨酸对大鼠学习记忆行为的影响[J]. 中国临床神经科学, 2016, 24(4): 371-375.
[19] Locci A, Porcu P, Talani G, et al. Neonatal estradiol exposure to female rats changes GABAA receptor expression and function, and spatial learning during adulthood[J]. Horm Behav, 2016, 87: 35-46.
[20] Li G, Lv J, Wang J, et al. GABAB receptors in the hippocampal dentate gyrus are involved in spatial learning and memory impairment in a rat model of vascular dementia[J]. Brain Res Bull, 2016, 124: 190-197.
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