Acupuncture has been applied in the treatment of Parkinson’s Disease (PD) in China for over decades. Clinical practice revealed that it could relieve the suf ferings of PD patients and improve their life quality. Bes...Acupuncture has been applied in the treatment of Parkinson’s Disease (PD) in China for over decades. Clinical practice revealed that it could relieve the suf ferings of PD patients and improve their life quality. Besides, acupuncture is a lso effective for other neurological disorders such as optic nerve atrophy, spin al cord injury and brain dysplasia. But the mechanism underlying the phenomenon is still unknow n. In the present study, we gave high and low frequency electroacupuncture (EA) stimulation to the medial forebrain bundle (MFB) transected rats in order to fi nd whether EA could attenuate the abnormal rotational behavior and dopaminergic neuron degeneration or increase the gene expression of GDNF and BDNF in the dopa minergic neurons. The main findings are: ① Transection of the MFB with a wire k nife resulted in abnormal ipsilateral rotational behavior of rats induced by amp hetamine and reduction of DA in the striatum to about 50% two weeks after the tr ansection. ② Both chronic low (2 Hz) and high (100 Hz) frequency EA stimulation were effective in attenuating the rotational behavior within 2 weeks of MFB tra nsection. The same effect could last for at least 4 weeks in the animals stimula ted with high frequency EA but not low frequency EA. ③ The content of DA in the striatum was increased significantly in the unlesioned side of both the low and high frequency EA stimulated rats. No increase had been found in the lesioned s ide. ④ High frequency EA could increase the gene expression of GDNF on the unle sioned side of substantia nigra reticular (SNr) region, and both sides of the gl obus pallidus, while low frequency EA was effective in increasing gene expressio n of GDNF in the unlesioned side of globus pallidus. ⑤ High frequency EA could attenuate the degeneration of dopaminergic neurons in the SNc. The low frequency EA had no effect. ⑥ High frequency EA, but not the low frequency, could increa se the gene expression of BDNF in the SNc and the ventral tegmental area (VTA) o f the lesioned side of rats after MFB transection, indicating that high frequenc y EA stimulation could be more effective than the low frequency EA in accelerati ng the synthesis of endogenous neurotrophic factors and in attenuating the degen eration of dopaminergic neurons.展开更多
Mitogen-activated protein kinase(MAPK)在成体脑细胞高度表达并参与了多种细胞功能活动的调节。近年来,本实验室的实验结果表明五型代谢型谷氨酸受体(mGluR5)可以激活纹状体培养神经元内MAPK的主要亚型ERK,ERK的激活经由两条独立的胞...Mitogen-activated protein kinase(MAPK)在成体脑细胞高度表达并参与了多种细胞功能活动的调节。近年来,本实验室的实验结果表明五型代谢型谷氨酸受体(mGluR5)可以激活纹状体培养神经元内MAPK的主要亚型ERK,ERK的激活经由两条独立的胞内信号通路介导,传统的IP3/Ca2+通路介导了一部分的ERK激活,而mGluR5的C-端结合蛋白Homer则以Ca2+-非依赖方式介导了主要的ERK激活。经两条通路激活的ERK可以协同刺激转录因子Elk-1和CREB,从而促进Elk-1和CREB敏感基因的表达。MAPK的分子生物学研究可以帮助我们了解谷氨酸受体信号转导、诱发性基因转录与表达以及神经元或突触的可塑性变化的分子机制。展开更多
文摘Acupuncture has been applied in the treatment of Parkinson’s Disease (PD) in China for over decades. Clinical practice revealed that it could relieve the suf ferings of PD patients and improve their life quality. Besides, acupuncture is a lso effective for other neurological disorders such as optic nerve atrophy, spin al cord injury and brain dysplasia. But the mechanism underlying the phenomenon is still unknow n. In the present study, we gave high and low frequency electroacupuncture (EA) stimulation to the medial forebrain bundle (MFB) transected rats in order to fi nd whether EA could attenuate the abnormal rotational behavior and dopaminergic neuron degeneration or increase the gene expression of GDNF and BDNF in the dopa minergic neurons. The main findings are: ① Transection of the MFB with a wire k nife resulted in abnormal ipsilateral rotational behavior of rats induced by amp hetamine and reduction of DA in the striatum to about 50% two weeks after the tr ansection. ② Both chronic low (2 Hz) and high (100 Hz) frequency EA stimulation were effective in attenuating the rotational behavior within 2 weeks of MFB tra nsection. The same effect could last for at least 4 weeks in the animals stimula ted with high frequency EA but not low frequency EA. ③ The content of DA in the striatum was increased significantly in the unlesioned side of both the low and high frequency EA stimulated rats. No increase had been found in the lesioned s ide. ④ High frequency EA could increase the gene expression of GDNF on the unle sioned side of substantia nigra reticular (SNr) region, and both sides of the gl obus pallidus, while low frequency EA was effective in increasing gene expressio n of GDNF in the unlesioned side of globus pallidus. ⑤ High frequency EA could attenuate the degeneration of dopaminergic neurons in the SNc. The low frequency EA had no effect. ⑥ High frequency EA, but not the low frequency, could increa se the gene expression of BDNF in the SNc and the ventral tegmental area (VTA) o f the lesioned side of rats after MFB transection, indicating that high frequenc y EA stimulation could be more effective than the low frequency EA in accelerati ng the synthesis of endogenous neurotrophic factors and in attenuating the degen eration of dopaminergic neurons.
文摘Mitogen-activated protein kinase(MAPK)在成体脑细胞高度表达并参与了多种细胞功能活动的调节。近年来,本实验室的实验结果表明五型代谢型谷氨酸受体(mGluR5)可以激活纹状体培养神经元内MAPK的主要亚型ERK,ERK的激活经由两条独立的胞内信号通路介导,传统的IP3/Ca2+通路介导了一部分的ERK激活,而mGluR5的C-端结合蛋白Homer则以Ca2+-非依赖方式介导了主要的ERK激活。经两条通路激活的ERK可以协同刺激转录因子Elk-1和CREB,从而促进Elk-1和CREB敏感基因的表达。MAPK的分子生物学研究可以帮助我们了解谷氨酸受体信号转导、诱发性基因转录与表达以及神经元或突触的可塑性变化的分子机制。
基金supported by the grant from the Saint Luke’s Hospital Foundation (Kansas City, MO, USA)grants (No. R01-DA010355, R01-MH061469) from the National Institutes of Health (Bethesda,MD, USA)
