Degeneration of the locus coeruleus noradrenergic system is thought to play a key role in the pathogenesis of Parkinson＇s disease （PD）, whereas pharmacological approaches to increase noradrenaline bioavailability m...Degeneration of the locus coeruleus noradrenergic system is thought to play a key role in the pathogenesis of Parkinson＇s disease （PD）, whereas pharmacological approaches to increase noradrenaline bioavailability may provide neuroprotection. Noradrenaline inhibits microglial activation and suppresses pro-inflamma- tory mediator production （e.g., tumor necrosis factor-a, interleukin-1β ＆ inducible nitric oxide synthase activity）, thus limiting the cytotoxicity of midbrain dopaminergic neurons in response to an inflamma- tory stimulus. Neighbouring astrocyte populations promote a neurotrophic environment in response to β2-adrenoceptor （β2-AR） stimulation via the production of growth factors （e.g., brain derived neurotrophic factor, cerebral dopamine neurotrophic factor ＆ glial cell derived neurotrophic factor which have shown promising neuroprotective and neuro-restorative effects in the nigrostriatal dopaminergic system. More recent findings have demonstrated a role for the β2-AR in down-regulating expression levels of the human a-synuclein gene SNCA and relative a-synuclein protein abundance. Given that a-synuclein is a major protein constituent of Lewy body pathology, a hallmark neuropathological feature in Parkinson＇s disease, these findings could open up new avenues for pharmacological intervention strategies aimed at alleviating the burden of a-synucleinopathies in the Parkinsonian brain. In essence, the literature reviewed herein supports our hypothesis of a tripartite neuroprotective role for noradrenaline in combating PD-related neuropathology and motor dysfunction via （1） inhibiting nigral microglial activation ＆ pro-inflammatory mediator production, （2） promoting the synthesis of neurotrophic factors from midbrain astrocytes and （3） downregulating a-synuclein gene expression and protein abundance in a β2-AR-dependent manner. Thus, taken together, either pharmacologically enhancing extra-synaptic noradrenaline bioavailability or targeting glial β2-ARs directly mak展开更多
目的为抑癌药物的临床研究建立人舌鳞癌动物模型.通过模拟与人体内环境及生物学特性相似的动物模型,观察肿瘤细胞的生物学、病理学行为及转移情况.方法选4～6周BALB/C-nu裸鼠,将体外培养的人舌鳞癌Cal27细胞接种于裸鼠右腋皮下,观察裸...目的为抑癌药物的临床研究建立人舌鳞癌动物模型.通过模拟与人体内环境及生物学特性相似的动物模型,观察肿瘤细胞的生物学、病理学行为及转移情况.方法选4～6周BALB/C-nu裸鼠,将体外培养的人舌鳞癌Cal27细胞接种于裸鼠右腋皮下,观察裸鼠体质量、皮下成瘤情况、肿瘤体积;待裸鼠体质量下降至原体质量的25%时,用颈椎脱臼法处死裸鼠,剥离瘤体组织进行解剖学观察及病理学观察.结果实验裸鼠在接种Cal27细胞第7～12 d后右腋下出现肿瘤,接种浓度为每只0.1 m L约2×10^6个细胞,成瘤率为86.7%.HE染色示肿瘤组织呈典型鳞癌表现;淋巴结及主要脏器未见转移.结论成功建立舌鳞癌Cal27裸鼠移植瘤模型.此动物模型能较客观地反映人舌鳞癌的生物学行为,为进行抑癌药物的临床研究与治疗打下良好基础.展开更多
基金Eoin O’Neill was supported by a Trinity College postgraduate award
文摘Degeneration of the locus coeruleus noradrenergic system is thought to play a key role in the pathogenesis of Parkinson＇s disease （PD）, whereas pharmacological approaches to increase noradrenaline bioavailability may provide neuroprotection. Noradrenaline inhibits microglial activation and suppresses pro-inflamma- tory mediator production （e.g., tumor necrosis factor-a, interleukin-1β ＆ inducible nitric oxide synthase activity）, thus limiting the cytotoxicity of midbrain dopaminergic neurons in response to an inflamma- tory stimulus. Neighbouring astrocyte populations promote a neurotrophic environment in response to β2-adrenoceptor （β2-AR） stimulation via the production of growth factors （e.g., brain derived neurotrophic factor, cerebral dopamine neurotrophic factor ＆ glial cell derived neurotrophic factor which have shown promising neuroprotective and neuro-restorative effects in the nigrostriatal dopaminergic system. More recent findings have demonstrated a role for the β2-AR in down-regulating expression levels of the human a-synuclein gene SNCA and relative a-synuclein protein abundance. Given that a-synuclein is a major protein constituent of Lewy body pathology, a hallmark neuropathological feature in Parkinson＇s disease, these findings could open up new avenues for pharmacological intervention strategies aimed at alleviating the burden of a-synucleinopathies in the Parkinsonian brain. In essence, the literature reviewed herein supports our hypothesis of a tripartite neuroprotective role for noradrenaline in combating PD-related neuropathology and motor dysfunction via （1） inhibiting nigral microglial activation ＆ pro-inflammatory mediator production, （2） promoting the synthesis of neurotrophic factors from midbrain astrocytes and （3） downregulating a-synuclein gene expression and protein abundance in a β2-AR-dependent manner. Thus, taken together, either pharmacologically enhancing extra-synaptic noradrenaline bioavailability or targeting glial β2-ARs directly mak
文摘目的为抑癌药物的临床研究建立人舌鳞癌动物模型.通过模拟与人体内环境及生物学特性相似的动物模型,观察肿瘤细胞的生物学、病理学行为及转移情况.方法选4～6周BALB/C-nu裸鼠,将体外培养的人舌鳞癌Cal27细胞接种于裸鼠右腋皮下,观察裸鼠体质量、皮下成瘤情况、肿瘤体积;待裸鼠体质量下降至原体质量的25%时,用颈椎脱臼法处死裸鼠,剥离瘤体组织进行解剖学观察及病理学观察.结果实验裸鼠在接种Cal27细胞第7～12 d后右腋下出现肿瘤,接种浓度为每只0.1 m L约2×10^6个细胞,成瘤率为86.7%.HE染色示肿瘤组织呈典型鳞癌表现;淋巴结及主要脏器未见转移.结论成功建立舌鳞癌Cal27裸鼠移植瘤模型.此动物模型能较客观地反映人舌鳞癌的生物学行为,为进行抑癌药物的临床研究与治疗打下良好基础.
