The goal of this study was to increase the dopamine content and reduce dopaminergic metabolites in the brain of Parkinson’s disease rats. Using high-performance liquid chromatography, we found that dopamine and dopam...The goal of this study was to increase the dopamine content and reduce dopaminergic metabolites in the brain of Parkinson’s disease rats. Using high-performance liquid chromatography, we found that dopamine and dopaminergic metabolite（dihydroxyphenylacetic acid and homovanillic acid） content in the midbrain of Parkinson’s disease rats was increased after neural stem cell transplantation ＋ Zhichan decoction, compared with neural stem cell transplantation alone. Our genetic algorithm results show that dihydroxyphenylacetic acid and homovanillic acid levels achieve global optimization. Neural stem cell transplantation ＋ Zhichan decoction increased dihydroxyphenylacetic acid levels up to 10-fold, while transplantation alone resulted in a 3-fold increment. Homovanillic acid levels showed no apparent change. Our experimental findings show that after neural stem cell transplantation in Parkinson’s disease rats, Zhichan decoction can promote differentiation of neural stem cells into dopaminergic neurons.展开更多
Current evidence shows that apolipoprotein E （APOE）, apolipoprotein CI （APOC1） and low density lipoprotein receptor-related protein （LRP） variations are related to late-onset Alzheimer＇s disease. However, it re...Current evidence shows that apolipoprotein E （APOE）, apolipoprotein CI （APOC1） and low density lipoprotein receptor-related protein （LRP） variations are related to late-onset Alzheimer＇s disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer＇s disease patients. We performed a 30-month longitudi- nal cohort study to investigate the relationship between Alzheimer＇s disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer＇s disease were recruit- ed form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess pa- tients＇ cognitive function. After a 30-month follow-up period, we found a significant reduction in Mini-Mental State Examination total score, a higher proportion of patients fulfilling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOE 4 carriers compared with non-carriers. In addition, the APOE 4 allele frequency was significantly higher in the cognitive impairment progression group compared with the non-cognitive im- pairment progression group. In conclusion, APOE e4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOE ~4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer＇s disease.展开更多
目的探讨大鼠大脑皮质梗死后同侧丘脑腹后外侧核（ventroposterior nucleus of the thalamus，VPN）组织蛋白酶B（cathepsinB，CatbB）的表达变化。方法成年雄性Sprague—Dawky大鼠随机分为假手术组和模型组，后者进一步分为术后1周组、...目的探讨大鼠大脑皮质梗死后同侧丘脑腹后外侧核（ventroposterior nucleus of the thalamus，VPN）组织蛋白酶B（cathepsinB，CatbB）的表达变化。方法成年雄性Sprague—Dawky大鼠随机分为假手术组和模型组，后者进一步分为术后1周组、2周组、3周组、4周组和8周组。电凝法闭塞大脑中动脉皮质支制作大脑皮质梗死模型。采用免疫组织化学染色和免疫荧光检测各时间点丘脑VPNCathB蛋白表达和细胞定位。结果大脑皮质梗死后丘脑VPNCathB表达水平逐渐增高，4周时达高峰，8周时下降，但仍然高于对照组（P均〈O．05）；可见CathB从溶酶体释放到细胞质。此外，在大脑皮质梗死后3周时，活化星形胶质细胞CathB表达水平也显著增高。结论大脑皮质梗死后1～8周期间，丘脑VPNCathB维持较高的表达水平，提示其可能在大脑皮质梗死后继发丘脑变性中起着一定的作用。展开更多
To prevent and treat Parkinson＇s disease in its early stages,it is essential to be able to detect the degree of early dopaminergic neuron degeneration.Dopamine transporters（DAT） in the striatum regulate synaptic do...To prevent and treat Parkinson＇s disease in its early stages,it is essential to be able to detect the degree of early dopaminergic neuron degeneration.Dopamine transporters（DAT） in the striatum regulate synaptic dopamine levels,and striatal ^99mTc-TRODAT-1 single-photon emission computed tomography（-SPECT） imaging is a marker for presynaptic neuronal degeneration.However,the association between the degree of dopaminergic degeneration and in vivo ^99mTc-TRODAT-1 SPECT imaging is unknown.Therefore,this study investigated the association between the degree of 6-hydroxydopamine（6-OHDA）-induced dopaminergic degeneration and DAT imaging using^99mTc-TRODAT-1 SPECT in rats.Different degrees of nigrostriatal dopamine depletion were generated by injecting different doses of 6-OHDA（2,4,and 8 μg） into the right medial forebrain bundle.The degree of nigrostriatal dopaminergic neuron degeneration was assessed by rotational behavior and immunohistochemical staining.The results showed that striatal ^99mTc-TRODAT-1 binding was significantly diminished both in the ipsilateral and the contralateral sides in the 4 and 8 μg 6-OHDA groups,and that DAT ^99mTc-TRODAT-1 binding in the ipsilateral striatum showed a high correlation to apomorphine-induced rotations at 8 weeks post-lesion（r = –0.887,P 〈 0.01）.There were significant correlations between DAT ^99mTc-TRODAT-1 binding in the ipsilateral striatum and the amount of tyrosine hydroxylase immunoreactive neurons in the ipsilateral substantia nigra in the 2,4,and 8 μg 6-OHDA groups at 8 weeks post-lesion（r = 0.899,P 〈 0.01）.These findings indicate that striatal DAT imaging using ^99mTc-TRODAT-1 is a useful technique for evaluating the severity of dopaminergic degeneration.展开更多
Charcot-Marie-Tooth disease type 1A（CMT1A） is caused by duplication of the peripheral myelin protein 22（PMP22） gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes melli...Charcot-Marie-Tooth disease type 1A（CMT1A） is caused by duplication of the peripheral myelin protein 22（PMP22） gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1 A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1 A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1 A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases.展开更多
基金financially supported by the National Natural Science Foundation of China,No.30772870
文摘The goal of this study was to increase the dopamine content and reduce dopaminergic metabolites in the brain of Parkinson’s disease rats. Using high-performance liquid chromatography, we found that dopamine and dopaminergic metabolite（dihydroxyphenylacetic acid and homovanillic acid） content in the midbrain of Parkinson’s disease rats was increased after neural stem cell transplantation ＋ Zhichan decoction, compared with neural stem cell transplantation alone. Our genetic algorithm results show that dihydroxyphenylacetic acid and homovanillic acid levels achieve global optimization. Neural stem cell transplantation ＋ Zhichan decoction increased dihydroxyphenylacetic acid levels up to 10-fold, while transplantation alone resulted in a 3-fold increment. Homovanillic acid levels showed no apparent change. Our experimental findings show that after neural stem cell transplantation in Parkinson’s disease rats, Zhichan decoction can promote differentiation of neural stem cells into dopaminergic neurons.
基金supported by the National Natural Science Foundation of China,No.81370445,81061120527,81241082Major Funding from Beijing Hospital,No.BJ-2010-30+4 种基金Key Project of Clinical Disciplines at the Subordinate Hospital,Ministry of Health,No.10120101National Department Public Benefit Research Foundation by the Ministry of Health,No.20130200812th 5-year National Program from Ministry of Scientific Technology,No.2012BAI10B01Science and Technology Development Foundation of Guangxi Zhuang Autonomous Region,No.1355005-62Canadian Institute of Health Research(CIHR),No.109606
文摘Current evidence shows that apolipoprotein E （APOE）, apolipoprotein CI （APOC1） and low density lipoprotein receptor-related protein （LRP） variations are related to late-onset Alzheimer＇s disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer＇s disease patients. We performed a 30-month longitudi- nal cohort study to investigate the relationship between Alzheimer＇s disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer＇s disease were recruit- ed form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess pa- tients＇ cognitive function. After a 30-month follow-up period, we found a significant reduction in Mini-Mental State Examination total score, a higher proportion of patients fulfilling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOE 4 carriers compared with non-carriers. In addition, the APOE 4 allele frequency was significantly higher in the cognitive impairment progression group compared with the non-cognitive im- pairment progression group. In conclusion, APOE e4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOE ~4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer＇s disease.
文摘目的探讨大鼠大脑皮质梗死后同侧丘脑腹后外侧核（ventroposterior nucleus of the thalamus，VPN）组织蛋白酶B（cathepsinB，CatbB）的表达变化。方法成年雄性Sprague—Dawky大鼠随机分为假手术组和模型组，后者进一步分为术后1周组、2周组、3周组、4周组和8周组。电凝法闭塞大脑中动脉皮质支制作大脑皮质梗死模型。采用免疫组织化学染色和免疫荧光检测各时间点丘脑VPNCathB蛋白表达和细胞定位。结果大脑皮质梗死后丘脑VPNCathB表达水平逐渐增高，4周时达高峰，8周时下降，但仍然高于对照组（P均〈O．05）；可见CathB从溶酶体释放到细胞质。此外，在大脑皮质梗死后3周时，活化星形胶质细胞CathB表达水平也显著增高。结论大脑皮质梗死后1～8周期间，丘脑VPNCathB维持较高的表达水平，提示其可能在大脑皮质梗死后继发丘脑变性中起着一定的作用。
基金supported by the National Natural Science Foundation of China,No.81571250
文摘To prevent and treat Parkinson＇s disease in its early stages,it is essential to be able to detect the degree of early dopaminergic neuron degeneration.Dopamine transporters（DAT） in the striatum regulate synaptic dopamine levels,and striatal ^99mTc-TRODAT-1 single-photon emission computed tomography（-SPECT） imaging is a marker for presynaptic neuronal degeneration.However,the association between the degree of dopaminergic degeneration and in vivo ^99mTc-TRODAT-1 SPECT imaging is unknown.Therefore,this study investigated the association between the degree of 6-hydroxydopamine（6-OHDA）-induced dopaminergic degeneration and DAT imaging using^99mTc-TRODAT-1 SPECT in rats.Different degrees of nigrostriatal dopamine depletion were generated by injecting different doses of 6-OHDA（2,4,and 8 μg） into the right medial forebrain bundle.The degree of nigrostriatal dopaminergic neuron degeneration was assessed by rotational behavior and immunohistochemical staining.The results showed that striatal ^99mTc-TRODAT-1 binding was significantly diminished both in the ipsilateral and the contralateral sides in the 4 and 8 μg 6-OHDA groups,and that DAT ^99mTc-TRODAT-1 binding in the ipsilateral striatum showed a high correlation to apomorphine-induced rotations at 8 weeks post-lesion（r = –0.887,P 〈 0.01）.There were significant correlations between DAT ^99mTc-TRODAT-1 binding in the ipsilateral striatum and the amount of tyrosine hydroxylase immunoreactive neurons in the ipsilateral substantia nigra in the 2,4,and 8 μg 6-OHDA groups at 8 weeks post-lesion（r = 0.899,P 〈 0.01）.These findings indicate that striatal DAT imaging using ^99mTc-TRODAT-1 is a useful technique for evaluating the severity of dopaminergic degeneration.
文摘Charcot-Marie-Tooth disease type 1A（CMT1A） is caused by duplication of the peripheral myelin protein 22（PMP22） gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1 A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1 A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1 A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases.
