慢性应激对大鼠行为学及脑神经颗粒素水平的影响及药物防治
|
摘要
目的探讨慢性应激对大鼠外显行为学变化的影响,检测体内儿茶酚胺类物质及神经颗粒素(Neurogranin,Ng)表达的变化及三七皂苷Rg1的防治效果。方法成年雄性SD大鼠36只,随机分为对照组(CON)、模型组(CUS)、和治疗组(CUS-G),采用慢性不可预见性应激方法建立慢性应激动物模型;采用旷场试验检测行为学变化,运用Morris水迷宫实验进行学习记忆力测试,使用放射免疫法检测血浆、脑组织儿茶酚胺类含量,Western blot法检测皮质、海马、下丘脑Ng含量。结果 6 w慢性应激后,实验组大鼠在水平运动和垂直运动方面得分均明显低于对照组与药物组,均P<0.05;水迷宫实验显示慢性应激后动物逃避潜伏期明显延长,而治疗组大鼠逃避潜伏期呈下降趋势(P<0.05);血浆、脑组织去甲肾上腺素与多巴胺在对照组、实验组与药物组间无明显变化;慢性应激大鼠皮质、海马、下丘脑Ng含量水平皆与模型大鼠有差异(P<0.05、P<0.01、P<0.05),治疗大鼠皮质、海马、下丘脑Ng含量亦皆与模型大鼠有差异(P<0.01、P<0.05、P<0.05)。结论慢性应激研究领域,神经颗粒素的敏感性优于单胺类神经递质,可作为敏感指标加以观察;100 mg/kg剂量的三七皂苷Rg1能够抑制应激所致学习记忆功能紊乱,对应激所致外显行为有积极的调节作用,对脑内神经颗粒素表达水平降低趋势有较好抑制作用。
Objective To investigate the effect of Ginsensode Rg1 on the expression of Neurogranin( Ng) in cortex,hippocampus and hypothalamus of rats with chronic stress model. Methods 36 adult male SD rats were randomly divided into control group( CON),model group( CUS),and treatment group( CUS-G). The chronic stress model was established by chronic unpredictable stress. The morris water maze was used to study the memory test. The expressions of DA and NE were detected by using radioimmunoassay. The content of Ng in cortex,hippocampus and hypothalamus was detected by Western blot. Results The water maze test showed that animal learning and memory ability decreased significantly after chronic stress,while the treatment group rats escape latency was significantly reduced,P < 0. 05; compared with control group,the content of DA and NE did not decrease significantly in model group( P > 0. 05). After 6 weeks of stress,rat cerebral cortex,hippocampus,hypothalamus Ng levels with chronic stress were significantly decreased compared with the model rats( P < 0. 05,P < 0. 01,P < 0. 05 respectively),the content of Ng content in cerebral cortex,hippocampus,hypothalamus were significantly increased with the model rat( P < 0. 01,P < 0. 05,P < 0. 05 respectively). Conclusions In chronic stress field,Ng is more sensitive than the monoamine neurotransmitters,it can be used as sensitive indicators to be observed. Chronic stress could change the behaviors of mice observably and the contents of Ng,the supplement of Ginsensode Rg1( 100 mg / kg) could come into being some interference effects.
Objective To investigate the effect of Ginsensode Rg1 on the expression of Neurogranin( Ng) in cortex,hippocampus and hypothalamus of rats with chronic stress model. Methods 36 adult male SD rats were randomly divided into control group( CON),model group( CUS),and treatment group( CUS-G). The chronic stress model was established by chronic unpredictable stress. The morris water maze was used to study the memory test. The expressions of DA and NE were detected by using radioimmunoassay. The content of Ng in cortex,hippocampus and hypothalamus was detected by Western blot. Results The water maze test showed that animal learning and memory ability decreased significantly after chronic stress,while the treatment group rats escape latency was significantly reduced,P < 0. 05; compared with control group,the content of DA and NE did not decrease significantly in model group( P > 0. 05). After 6 weeks of stress,rat cerebral cortex,hippocampus,hypothalamus Ng levels with chronic stress were significantly decreased compared with the model rats( P < 0. 05,P < 0. 01,P < 0. 05 respectively),the content of Ng content in cerebral cortex,hippocampus,hypothalamus were significantly increased with the model rat( P < 0. 01,P < 0. 05,P < 0. 05 respectively). Conclusions In chronic stress field,Ng is more sensitive than the monoamine neurotransmitters,it can be used as sensitive indicators to be observed. Chronic stress could change the behaviors of mice observably and the contents of Ng,the supplement of Ginsensode Rg1( 100 mg / kg) could come into being some interference effects.
引文
[1]Zhongming LI,Jinghua LI,Zhiming Wang,et al.L-tyrosine improves neuroendocrine function in a mouse model of chronic stress[J].Neural Regeneration Research,2012,7(18):1413-1419.
[2]Pohlack ST,Nees F,Ruttorf M,et al.Risk variant for schizophrenia in the neurogranin gene impacts on hippocampus activation during contextual fear conditioning[J].Psychiatry,2011,16(11):1072-1073.
[3]Huang KP,Huang FL,Jager T,et al.Neurogranin/RC3 enhances long-term potentiation and learning by promoting calcium-mediatedSignaling[J].J Neurosci,2004,24:10660-10669.
[4]宋晓斌,何波,陈鹏,等.三七皂苷Rg1对动物学习记忆功能的影响及其机理研究[J].昆明医学院学报,2010,(6):21-27.
[5]黄小平,邓常清,邱咏园,等.黄芪甲苷和三七的三种有效成分配伍对小鼠脑缺血/再灌注后氧化应激和Nrf2/HO-1途径的影响[J].中国药理学通报,2013,29(11):1596-1601.
[6]孙晓飞,廖华,杨琨脉,等.冲噪声暴露后大鼠听皮质神经颗粒素的表达研究[J].Journal of Audiology and Speech Pathology,2012,20(3):250-253.
[7]郭超峰,张琢,银胜高,等.合欢花总黄酮对抑郁模型大鼠学习记忆能力的影响[J].中药药理与临床,2013,5:61-64.
[8]Quan M,Zheng C,Zhang N,et al.Impairments of behavior,information flow between thalamus and cortex,and prefrontal cortical synaptic plasticity in an animal model of depression[J].Brain Res Bull,2011,85:109-116.
[9]Donnelly E.Work-related stress and posttraumatic stress in emergency medical services[J].Prehosp Emerg Care,2012,1601:76-85.
[10]Palanisamy A,Baxter MG,Keel PK,et al.Rats exposed to isoflurane in utero during early gestation are behaviorally abnormal as adults[J].Anesthesiology,2011,114:521-528.
[11]Kelsey L,Clark D,Behrad T.The role of prefrontal catecholamines in attention and working memory[J].Front Neural Circuits,2014,(8):142-155.
[12]Andrew J,Nelson D,Molly T,et al.The effect of catecholaminergic depletion within the prelimbic and infralimbic medial prefrontal cortex on recognition memory for recency,location,and objects[J].Behav Neurosci,2011,125(3):396-403.
[13]Kvetnansky R,Ukropec J,Laukova M,et al.Stress stimulates production of catecholamines in rat adipocytes[J].Cell Mol Neurobiol,2012,32(5):801-813.
[14]Jane Kovalevich,Gladys Corley,William Yen,et al.Cocaine decreases expression of neurogranin via alterations in thyroid receptor/retinoid X receptor signaling[J].J Neurochem,2012,121(2):302-313.
[15]Bruce Wang,Matthias Wabl,Finn Skou Pedersen,et al.Activation of the brain-specific neurogranin gene in murine T-cell lymphomas by proviral insertional mutagenesis[J].Gene,2009,442(1-2):55-62.
[16]Freesia L,Huang F,Kuo-Ping.Methylphenidate improves the behavioral and cognitive deficits of neurogranin knockout mice[J].Genes Brain Behav,2012,11(7):794-805.
[17]Ling Zhong,Nashaat Z,Gerges G.Neurogranin and synaptic plasticity.balance[J].Commun Integr Biol,2010,3(4):340-342.
[18]Kuo-Ping Huang,Freesia L.Calcium-sensitive translocation of calmodulin and neurogranin between soma and dendrites of mouse hippocampal CA1neurons[J].Chem Neurosci,2011,2(4):223-230.
[19]Seung-Hyuk,Chung C,Hassan Marzban.Aldinger Zac1 plays a key role in the development of specific neuronal subsets in the mouse cerebellum[J].Neural Dev,2011,18:1186-1197.
[20]Zhong L,Kaleka KS,Gerges NZ.Neurogranin phosphorylation finetunes long-term potentiation[J].Eur J Neurosci,2011,33:244-250.
[2]Pohlack ST,Nees F,Ruttorf M,et al.Risk variant for schizophrenia in the neurogranin gene impacts on hippocampus activation during contextual fear conditioning[J].Psychiatry,2011,16(11):1072-1073.
[3]Huang KP,Huang FL,Jager T,et al.Neurogranin/RC3 enhances long-term potentiation and learning by promoting calcium-mediatedSignaling[J].J Neurosci,2004,24:10660-10669.
[4]宋晓斌,何波,陈鹏,等.三七皂苷Rg1对动物学习记忆功能的影响及其机理研究[J].昆明医学院学报,2010,(6):21-27.
[5]黄小平,邓常清,邱咏园,等.黄芪甲苷和三七的三种有效成分配伍对小鼠脑缺血/再灌注后氧化应激和Nrf2/HO-1途径的影响[J].中国药理学通报,2013,29(11):1596-1601.
[6]孙晓飞,廖华,杨琨脉,等.冲噪声暴露后大鼠听皮质神经颗粒素的表达研究[J].Journal of Audiology and Speech Pathology,2012,20(3):250-253.
[7]郭超峰,张琢,银胜高,等.合欢花总黄酮对抑郁模型大鼠学习记忆能力的影响[J].中药药理与临床,2013,5:61-64.
[8]Quan M,Zheng C,Zhang N,et al.Impairments of behavior,information flow between thalamus and cortex,and prefrontal cortical synaptic plasticity in an animal model of depression[J].Brain Res Bull,2011,85:109-116.
[9]Donnelly E.Work-related stress and posttraumatic stress in emergency medical services[J].Prehosp Emerg Care,2012,1601:76-85.
[10]Palanisamy A,Baxter MG,Keel PK,et al.Rats exposed to isoflurane in utero during early gestation are behaviorally abnormal as adults[J].Anesthesiology,2011,114:521-528.
[11]Kelsey L,Clark D,Behrad T.The role of prefrontal catecholamines in attention and working memory[J].Front Neural Circuits,2014,(8):142-155.
[12]Andrew J,Nelson D,Molly T,et al.The effect of catecholaminergic depletion within the prelimbic and infralimbic medial prefrontal cortex on recognition memory for recency,location,and objects[J].Behav Neurosci,2011,125(3):396-403.
[13]Kvetnansky R,Ukropec J,Laukova M,et al.Stress stimulates production of catecholamines in rat adipocytes[J].Cell Mol Neurobiol,2012,32(5):801-813.
[14]Jane Kovalevich,Gladys Corley,William Yen,et al.Cocaine decreases expression of neurogranin via alterations in thyroid receptor/retinoid X receptor signaling[J].J Neurochem,2012,121(2):302-313.
[15]Bruce Wang,Matthias Wabl,Finn Skou Pedersen,et al.Activation of the brain-specific neurogranin gene in murine T-cell lymphomas by proviral insertional mutagenesis[J].Gene,2009,442(1-2):55-62.
[16]Freesia L,Huang F,Kuo-Ping.Methylphenidate improves the behavioral and cognitive deficits of neurogranin knockout mice[J].Genes Brain Behav,2012,11(7):794-805.
[17]Ling Zhong,Nashaat Z,Gerges G.Neurogranin and synaptic plasticity.balance[J].Commun Integr Biol,2010,3(4):340-342.
[18]Kuo-Ping Huang,Freesia L.Calcium-sensitive translocation of calmodulin and neurogranin between soma and dendrites of mouse hippocampal CA1neurons[J].Chem Neurosci,2011,2(4):223-230.
[19]Seung-Hyuk,Chung C,Hassan Marzban.Aldinger Zac1 plays a key role in the development of specific neuronal subsets in the mouse cerebellum[J].Neural Dev,2011,18:1186-1197.
[20]Zhong L,Kaleka KS,Gerges NZ.Neurogranin phosphorylation finetunes long-term potentiation[J].Eur J Neurosci,2011,33:244-250.