目的研究岛叶GABAB_2受体(GABAB_2R)在匹罗卡品致痫大鼠再认记忆功能损害中的作用。方法选用SPF级雄性SD大鼠,建立氯化锂-匹罗卡品癫痫模型。恢复1周后,将建模成功的大鼠随机分成岛叶组(GI)、嗅周皮质组(PHR)、海马组(HP)、岛叶对照组(G...目的研究岛叶GABAB_2受体(GABAB_2R)在匹罗卡品致痫大鼠再认记忆功能损害中的作用。方法选用SPF级雄性SD大鼠,建立氯化锂-匹罗卡品癫痫模型。恢复1周后,将建模成功的大鼠随机分成岛叶组(GI)、嗅周皮质组(PHR)、海马组(HP)、岛叶对照组(GI-X)、嗅周皮质对照组(PHR-X)和海马溶媒对照组(HP-X)及正常对照组(Control)共7组,每组10只。立体定位下分别于岛叶、嗅周皮质和海马注射GABAB_2R si RNA腺相关病毒颗粒(HBAAV2/9-GABAB_2R si RNA)和空载体腺相关病毒颗粒,正常组注射同等体积的生理盐水。Intelli Cage全自动智能监测系统持续观察大鼠再认记忆功能的改变,并用免疫印迹实验和荧光免疫实验检测GABAB_2R蛋白表达情况。结果 GI组的鼻触次数和访问次数均高于GI-X组(P均<0.05);GI组的鼻触次数和访问次数均高于Control组(P均<0.05);PHR组的鼻触次数和访问次数均高于PHR-X组和Control组(P均<0.05);HP组的鼻触次数和访问次数均高于HP-X组和Control组(P均<0.05)。结论岛叶GABAB_2受体活性水平的降低有助于改善致痫大鼠再认记忆功能。展开更多
Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which l...Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which leads to intellectual disability and social impairment. γ-aminobutyric acid （GABA） is the major inhibitory neuro- transmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, suggesting the role of GABAB receptor on FMRP regulation. Here we investi- gated the signaling events linking the GABAB receptor and FMRP. Methods Western blot was used in this study to detect protein expression and kinase phosphorylation in cerebellar granule neurons. For key molecules in signal- ling pathway, RNAi was used in MEFs to confirm the results in neurons. Results GABAB receptor activation up- regulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms： the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. Conclusion These results suggest a role for GABAB receptor in Fmrp regulation and a po- tential interest of GABAB receptor signaling in FXS improvement.展开更多
Aim To investigate the mechanisms underlying depressive-like behavior induced by chronic cerebral is- chemia in rats. Methods In the present study, a chronic cerebral hypoperfusion model was established by perma- 2VO...Aim To investigate the mechanisms underlying depressive-like behavior induced by chronic cerebral is- chemia in rats. Methods In the present study, a chronic cerebral hypoperfusion model was established by perma- 2VO） in rats. Two weeks after 2VO, GAB- nent bilateral common carotid arteries occlusion （two-vessel occlusion, AB receptor agonist baclofen （25 mg · kg^-1 . d^-1 i p ） was administrated for 21 days. The FST was performed to evaluate depressive-like behavior in which the immobility time was recorded. In addition, the expression of brain derived neurotrophic factor （BDNF） in hippocampal CA1 was measured by Western blot. Results The immobility time of 2VO group was significantly prolonged and the expression of BDNF was decreased by 28.95% compared with sham group. After activation of GABAB receptors by baclofen, the immobility time was significantly reduced and the expression of BDNF was increased by 47.91% compared with 2VO group. Conclusion 2VO induced ob- vious depressive-like behavior in rats. Activation of GABAB receptors alleviates the depressive-like behavior in- duced by chronic cerebral ischemia via upredulation of BDNF in hippocampal CA1 in rats.展开更多
Objectives: To investigate the potential role of GABAB Receptors (GABABRs) involved in the effect of Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM) treatment on precocious puberty. Methods: Female Spr...Objectives: To investigate the potential role of GABAB Receptors (GABABRs) involved in the effect of Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM) treatment on precocious puberty. Methods: Female Sprague-Dawley rats were randomly divided into four groups: normal (N), central precocious puberty (CPP) model (M), CPP fed with normal saline (S) and CPP fed with Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM). Rats of postnatal day 5 were given a single subcutaneous injection of 240 μg danazol to establish CPP model rats. Rats of S and TCM groups were continuously administered with saline or nourishing “Yin”-removing “Fire” Chinese herb mixture since postnatal day 15. The expression of GABABRs was detected by means of real-time PCR and immunohistochemistry. Results: The expression of hypothalamic GnRH mRNA in M was significantly increased on the day of pre-puberty when compared with that of N (P < 0.01). On the day of onset-puberty, LH levels were higher in M than those in N (P < 0.01), while the serum E2 and LH levels of TCM decreased when compared with those of M (P <sub>B1</sub> receptor (GABABR1) immunoreactive cells in the arcuate nucleus (ARN) was decreased in M when compared with that of N (P < 0.05) and increased in TCM compared with that of M (P < 0.05);simultaneously, the expression of GABABR1 mRNA in hypothalamus was significantly decreased in M when compared with that of N (P < 0.01) and increased in TCM compared with that of M (P < 0.01). On the day of onset-puberty, the number of GABABR1 immunoreactive cells in medial septum (MS) was decreased in M compared with that in N (P < 0.05) and increased in TCM comparing with that of M (P < 0.05);meanwhile, the mRNA expression of GABABR1 in hypothalamus was decreased in M compared with that in N (P <sub>B2</sub> receptor (GABABR2) immunoreactive cells in the ARN, MS and diagnonal band of broca (DBB) were decreased in M when compared with those of N (P < 0.05) and increased in TCM compared with those of M (P < 0.05) on the day of onset-puberty. At the same time, the mRNA expression of GABABR2 was significantly decreased in M compared with that of N (P < 0.01). Conclusions: These results indicated that the GABABRs might involve in the curative effect of Nourishing “Yin”-Removing “Fire” Chinese herbal mixture on CPP rats.展开更多
文摘目的研究岛叶GABAB_2受体(GABAB_2R)在匹罗卡品致痫大鼠再认记忆功能损害中的作用。方法选用SPF级雄性SD大鼠,建立氯化锂-匹罗卡品癫痫模型。恢复1周后,将建模成功的大鼠随机分成岛叶组(GI)、嗅周皮质组(PHR)、海马组(HP)、岛叶对照组(GI-X)、嗅周皮质对照组(PHR-X)和海马溶媒对照组(HP-X)及正常对照组(Control)共7组,每组10只。立体定位下分别于岛叶、嗅周皮质和海马注射GABAB_2R si RNA腺相关病毒颗粒(HBAAV2/9-GABAB_2R si RNA)和空载体腺相关病毒颗粒,正常组注射同等体积的生理盐水。Intelli Cage全自动智能监测系统持续观察大鼠再认记忆功能的改变,并用免疫印迹实验和荧光免疫实验检测GABAB_2R蛋白表达情况。结果 GI组的鼻触次数和访问次数均高于GI-X组(P均<0.05);GI组的鼻触次数和访问次数均高于Control组(P均<0.05);PHR组的鼻触次数和访问次数均高于PHR-X组和Control组(P均<0.05);HP组的鼻触次数和访问次数均高于HP-X组和Control组(P均<0.05)。结论岛叶GABAB_2受体活性水平的降低有助于改善致痫大鼠再认记忆功能。
文摘Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which leads to intellectual disability and social impairment. γ-aminobutyric acid （GABA） is the major inhibitory neuro- transmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, suggesting the role of GABAB receptor on FMRP regulation. Here we investi- gated the signaling events linking the GABAB receptor and FMRP. Methods Western blot was used in this study to detect protein expression and kinase phosphorylation in cerebellar granule neurons. For key molecules in signal- ling pathway, RNAi was used in MEFs to confirm the results in neurons. Results GABAB receptor activation up- regulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms： the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. Conclusion These results suggest a role for GABAB receptor in Fmrp regulation and a po- tential interest of GABAB receptor signaling in FXS improvement.
文摘Aim To investigate the mechanisms underlying depressive-like behavior induced by chronic cerebral is- chemia in rats. Methods In the present study, a chronic cerebral hypoperfusion model was established by perma- 2VO） in rats. Two weeks after 2VO, GAB- nent bilateral common carotid arteries occlusion （two-vessel occlusion, AB receptor agonist baclofen （25 mg · kg^-1 . d^-1 i p ） was administrated for 21 days. The FST was performed to evaluate depressive-like behavior in which the immobility time was recorded. In addition, the expression of brain derived neurotrophic factor （BDNF） in hippocampal CA1 was measured by Western blot. Results The immobility time of 2VO group was significantly prolonged and the expression of BDNF was decreased by 28.95% compared with sham group. After activation of GABAB receptors by baclofen, the immobility time was significantly reduced and the expression of BDNF was increased by 47.91% compared with 2VO group. Conclusion 2VO induced ob- vious depressive-like behavior in rats. Activation of GABAB receptors alleviates the depressive-like behavior in- duced by chronic cerebral ischemia via upredulation of BDNF in hippocampal CA1 in rats.
文摘Objectives: To investigate the potential role of GABAB Receptors (GABABRs) involved in the effect of Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM) treatment on precocious puberty. Methods: Female Sprague-Dawley rats were randomly divided into four groups: normal (N), central precocious puberty (CPP) model (M), CPP fed with normal saline (S) and CPP fed with Nourishing “Yin”-Removing “Fire” Chinese herb mixture (TCM). Rats of postnatal day 5 were given a single subcutaneous injection of 240 μg danazol to establish CPP model rats. Rats of S and TCM groups were continuously administered with saline or nourishing “Yin”-removing “Fire” Chinese herb mixture since postnatal day 15. The expression of GABABRs was detected by means of real-time PCR and immunohistochemistry. Results: The expression of hypothalamic GnRH mRNA in M was significantly increased on the day of pre-puberty when compared with that of N (P < 0.01). On the day of onset-puberty, LH levels were higher in M than those in N (P < 0.01), while the serum E2 and LH levels of TCM decreased when compared with those of M (P <sub>B1</sub> receptor (GABABR1) immunoreactive cells in the arcuate nucleus (ARN) was decreased in M when compared with that of N (P < 0.05) and increased in TCM compared with that of M (P < 0.05);simultaneously, the expression of GABABR1 mRNA in hypothalamus was significantly decreased in M when compared with that of N (P < 0.01) and increased in TCM compared with that of M (P < 0.01). On the day of onset-puberty, the number of GABABR1 immunoreactive cells in medial septum (MS) was decreased in M compared with that in N (P < 0.05) and increased in TCM comparing with that of M (P < 0.05);meanwhile, the mRNA expression of GABABR1 in hypothalamus was decreased in M compared with that in N (P <sub>B2</sub> receptor (GABABR2) immunoreactive cells in the ARN, MS and diagnonal band of broca (DBB) were decreased in M when compared with those of N (P < 0.05) and increased in TCM compared with those of M (P < 0.05) on the day of onset-puberty. At the same time, the mRNA expression of GABABR2 was significantly decreased in M compared with that of N (P < 0.01). Conclusions: These results indicated that the GABABRs might involve in the curative effect of Nourishing “Yin”-Removing “Fire” Chinese herbal mixture on CPP rats.
