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tyrosine hydroxylase expression in the midbrain of Parkinson's disease model rats treated with Xifeng Dingchan decoction

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Neural Regeneration Research 2011年第12期6卷 914-918页

作者： Enli Luo First Department of Neurology the Second Clinical Medical College Guangzhou University of Traditional Chinese Medicine Guangzhou 510120 Guangdong Province China Post-doctoral Research Station Guangzhou University of Traditional Chinese Medicine Guangzhou 510006 Guangdong Province China

This study showed that abnormal behavioral changes were greatly improved in rats displaying Parkinson＇s disease-like symptoms after intragastric administration of Xifeng Dingchan decoction at 15, 7.5, 3.75 g/kg per day. In addition, tyrosine hydroxylase mRNA expression in the substantia nigra of the midbrain was up-regulated, and tyrosine hydroxylase content in the midbrain ventral tegmentum and substantia nigra pars compacta was also increased. The effect of administration of Xifeng Dingchan decoction at 7.5 g/kg per day was similar to that of Madopar at 67.5 mg/kg per day. These results indicate that the therapeutic effect of Xifeng Dingchan decoction on Parkinson＇s disease is associated with the up-regulated protein and mRNA expression of tyrosine hydroxylase in the midbrain.

关键词： Parkinson's disease Xifeng Dingchan decoction tyrosine hydroxylase midbrain behavior Chinese herbal medicine neural regeneration

A core-satellite-like nanoassembly reverses a decisive tyrosine hydroxylase loss in degenerative dopaminergic neurons

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Nano Research 2023年第7期16卷 9835-9847页

作者： Ke Yao Jiamin Gan Di Zhao Mingding Li Xiaoquan Shen Yumin Yang Peijian Feng Qundong Shen Department of Polymer Science&Engineering and Key Laboratory of High-Performance Polymer Materials and Technology of MOE School of Chemistry&Chemical EngineeringNanjing UniversityNanjing 210023China Key Laboratory for Neuroregeneration of Jiangsu Province and Ministry of Education Co-innovation Center of NeuroregenerationNantong UniversityNantong 226001China Medical School of Nanjing University Nanjing 210008China State Key Laboratory of Analytical Chemistry for Life Science Nanjing UniversityNanjing 210023China

In recent years,neurodegenerative diseases,such as Parkinson’s or Alzheimer’s diseases,are rapidly rising in *** main hallmark of Parkinson’s disease is the falling levels of neurotransmitter dopamine in the mid-brain with dopaminergic neurons *** therapeutic solutions,including drugs,deep brain stimulation,and cell transplantation,can only alleviate the symptoms of Parkinson’s *** is a tremendous challenge to reverse the function degeneration of the crucial dopaminergic ***,we develop a core-satellite-like nanoassembly(PDA-AFn(by integrating polydopamine nanoparticles and apoferritin))to raise the expression of tyrosine hydroxylase(TH),a rate-limiting enzyme in the formation of the *** components in the nanoassembly could cooperate with each other,not only elaborately regulate the iron homeostasis and redox microenvironment,but also utilize excessive reactive oxygen species(ROS)and iron ions in the damaged neurons to supply extra dopamine and enhance TH activity,and consequently restore the function of the degenerated ***,the nanoassembly-treatment relieves the dyskinesia and dramatical increases the tyrosine hydroxylase and dopamine level in the midbrain of Parkinson’s disease model *** is an explicit yet inspiring advance in treatment of the neurodegeneration.

关键词： neurodegenerative disease dopaminergic neurons tyrosine hydroxylase apoferritin Parkinson’s disease

Dark rearing maintains tyrosine hydroxylase expression in retinal amacrine cells following optic nerve transection

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Neural Regeneration Research 2012年第1期7卷 18-23页

作者： Wei Wan Zhenghai Liu Xiaosheng Wang Xuegang Luo Department of Human Anatomy and Neurobiology Xiangya Medical College of Central South University Changsha 410013 Hunan Province China Department of Human Anatomy University of South China Hengyang 421001 Hunan Province China

The present study examined changes in retinal tyrosine hydroxylase （TH） expression in rats having undergone optic nerve transection and housed under a normal day/night cycle or in the dark. The aim was to investigate the effects of amacrine cells on axonal regeneration in retinal ganglion cells and on the synapses that transmit visual signals. The results revealed that retinal TH expression gradually decreased following optic nerve transection in rats housed under a normal day/night cycle reaching a minimum at 5 days. In contrast, retinal TH expression decreased to a minimum at 1 day following optic nerve transection in dark reared rats, gradually increasing afterward and reaching a normal level at 5 7 days. The number of TH-positive synaptic particles correlated with the TH levels indicating that dark rearing can help maintain TH expression during the synaptic degeneration stage （5 7 days after optic nerve injury） in retinal amacrine cells.

关键词： optic nerve transection tyrosine hydroxylase dark rearing amacrine cells peripheral nerve injury neural regeneration

Treatment time influences the effects of a low-frequency pulsed electric field on synthesis of tyrosine hydroxylase and dopamine in PC12 cells

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Neural Regeneration Research 2010年第4期5卷 291-294页

作者： Hongfeng Zhang Yuanzhang Fang Ying Liu Hongxing Qi School of Life Science East China Normal University Shanghai 200062 China Key Laboratory of Optical and Magnetic Resonance Spectroscopy Department of Physics East China Normal University Shanghai 200062 China

BACKGROUND： Electromagnetic radiation can influence dopamine （DA） synthesis in brain tissues or ceils, but electromagnetic frequencies, intensities, and radiation time can produce different effects. In addition, the signal pathway by which electromagnetic radiation influences DA synthesis remains controversial. OBJECTIVE： To determine tyrosine hydroxylase （TH） expression in PC12 cells and DA levels in cell culture media after different periods of low-frequency pulsed electric field （LF-PEF） stimulation, and to determine how LF-PEF signaling stimulates TH synthesis using inhibitors. DESIGN, TIME AND SETTING： A parallel, controlled, cell experiment was performed at the Laboratory of Cell Biology, School of Life Science, East China Normal University, between January and October 2006. MATERIALS： PC12 cells were purchased from the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, China. Nerve growth factor was purchased from PeproTech, USA. The protein kinase A inhibitor, H-89, and mitogen-activated protein kinase kinase inhibitor, U0126, were purchased from Sigma, USA. METHODS：（1） Following routine culture in Dulbecco＇s modified eagle medium, primary PC12 cells were stimulated under LF-PEF （pulse frequency ***, pulse width 20 μs, peak field strength 1 V/m） for 5, 10, 15, 20, and 30 minutes. （2） Inhibitors （H-89 or U0126, 1 μmol/L） were added 30 minutes before LF-PEF stimulation for 10 minutes. MAIN OUTCOME MEASURES：（1） TH expression was determined by Western blot in PC12 cells at 0.5, 1,2, 3, and 4 days after LF-PEF stimulation. Similarly, DA was measured by high-performance liquid chromatography in media at 2, 3, 4, or 5 days after LF-PEE （2） TH expression was detected 1 day after H-89 or U0126 treatment and LF-PEE RESULTS：（1） Short-term LF-PEF stimulation （5 and 10 minutes） increased TH expression and media DA levels after short-term culture （2 days）（P 〈 0.01）, but both parameters decreased with longer culture （3 4 days）（P 〈 0.01

关键词： low-frequency pulsed electric field PC12 cells tyrosine hydroxylase dopamine protein kinase A pathway Ras/mitogen-activated protein kinase kinase 1/2 pathway

tyrosine hydroxylase gene transfections to different sites of striatum in the rat model of Parkinson’s disease

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Open Journal of Genetics 2013年第2期3卷 30-37页

作者： Atso Raasmaja Sarka Lehtonen Tiina Kaariainen Pasi Lampela Marko Huotari Anne Lecklin Division of Pharmacology&Toxicology University of HelsinkiHelsinkiFinland Department of Pharmacy University of Eastern FinlandKuopioFinland

The use of gene therapy has been intensively studied as a potential method to treat Parkinson’s disease (PD) and other degenerative brain diseases. However, the effects of experimental measures and approaches on the outcome of gene delivery or on the physiological state of target tissues have not been analyzed as much and systematically. Therefore, we have infused adenovirus vectors expressing either a therapeutic tyrosine hydroxylase (TH) gene or a lacZ reporter gene into striatum in a rat model of PD. The experimental procedures were tested using the Ad lacZ vector in order to optimize concentrations, volumes, infusion speeds and transfection times. The expression of Ad lacZ vector was lower and declined earlier in the lesioned than unlesioned striatum suggesting that the lesion affects on the transfection efficiency and outcome of gene transfection. The effect of three different approaches of Ad TH vector transfection was compared: 1) the delivery of Ad TH gene vector alone into one single site of striatum, 2) the delivery of Ad TH gene vector alone into multiple sites of striatum, and 3) the delivery of Ad TH gene vector into one site of striatum followed by a continuous infusion of tetrahydrobiopterin (BH4) cofactor with a mini pump. There was a small and transient unsignificant decrease in the turning behavior when the Ad TH vector was delivered into one site of the striatum. Simultaneous infusion into several sites or together with BH4 cofactor did not improve more the effect of gene delivery. Thus, although the effects were unsignificant, the Ad TH transfection seemed to decrease the turning behavior in the rat model of PD and the optimal effect was seen at some specific doses and time points. Furthermore, the outcome of gene therapy could depend in addition to the amount and efficacy of gene vectors also on the physiological state and experimental strategies.

关键词： tyrosine hydroxylase Tetrahydrobiopterin Adenovirus Vector 6-Hydroxydopamine Parkinson’s Disease Gene Therapy

Effect of Bushen Huoxue Decoction(补肾活血饮) on the Orphan Receptor and tyrosine hydroxylase in the Brain of Rats with Parkinson's Disease

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Chinese Journal of Integrative Medicine 2011年第1期17卷 43-47页

作者：杨明会王海明刘毅 Institute of Traditional Chinese Medicine General Hospital of PLA

Objective：To explore the effect of Bushen Huoxue Decoction（补肾活血饮,BHD） on the orphan receptor（Nurr1） and tyrosine hydroxylase（TH） in the brain of rats with Parkinson＇s disease（PD）.Methods：One hundred and twenty SD rats were divided into 100 in the model group and 20 in the normal control group,fifty-eight SD rats from the model group,established into PD model successfully by injuring their substantia nigra （SSN） with 6-hydroxydopamine,were divided equally into the model group and the test group,and they were treated with saline and BHD,respectively,for eight successive *** change in the rats＇ behavior before and after treatment was observed by counting the cycles of rotation induced by apomorphine injection; the pathology of neurons,level of Nurr1 mRNA expression,and amount of TH positive cells in SSN were observed after ***：The rats＇ behavior was improved in the tested group significantly,the rotation cycle after treatment being 84.0±20.0 cycles/40 min,which was significantly lower than that in the model group（377.0±62.3 cycles/40 min,P〈0.01）.Besides,the Nurr1 mRNA expression and TH positive cell in the test group were 0.97±0.15 and 49.40±14.72,respectively,which were significantly higher than those in the model group,0.22±0.03 and 5.45±2.58,respectively（all P〈0.01）.Conclusion：BHD could treat PD by enhancing the Nurr1 mRNA expression,increasing the TH content in brain,and promoting the repairing of injured neuron in cerebral SSN.

关键词： Parkinson's disease Bushen Huoxue Decoction Chinese medicine Orphan receptor tyrosine hydroxylase

Effect of Acupuncture on Contents of tyrosine hydroxylase and Glial Fibrillary Acidic Protein in Ventral Tegmental Area of Heroin Self-administrating Rats

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Journal of Acupuncture and Tuina Science 2006年第1期4卷 7-12,F0002页

作者：朱忠春胡军徐平 Shanghai Institute of Acupuncture and Meridian Shanghai 200030P.R.China Shanghai University of TCM Shanghai 201203P.R.China

Objective： This present study is to investigate the biochemical adaptations in the rdated brain regions of the mesolimbic dopamine system, such as the ventral tegmental area （VFA）, nucleus accumbens （NAc）, amygdale （Amy）, prefrontal cortex （PFC） , substantia nigra （SN） and caudateputamen （CPu） in response to heroin self-administration in rats and observe the effect of electroacupuncture on them. Methods. Thirty rats were trained by nose-poking response to establish stable intravenous heroin self-administration within 14 days, and then divided randomly into model group （group B） including 6 rats, withdrawal group which were withdrawn from heroin for 1 week （group C, n = 6） and for 2 weeks （group D, n= 6）, during which time they only lived in their individual home cages, and dectrtyacupuncture group which were also withdrawn from heroin for 1 week （group E, n= 6） and for 2 weeks （group F, n = 6）, during which time they were given electro-acupuncture treatment for 20 min daily and then returned to their individual home cages; in the meantime, another 6 rats were trained by nose-poking response with saline for 14 days as control （group A）; Then the leeds of tyrosine hydroxylase （TH） and glial fibrillary acidic protein （GFAP） in VFA, NAc, Amy, PFC, SN, CPu were detected with immunohistochemistry method. Results. The leeds of TH and GFAP in VFA of the heroin self administrating rats were obviously increased, and the leeds of TH and GFAP in NAc were also decreased, and these changes were not found in SN, CPu, Amy and PFC; Electro-acupuncture could promote the up regulation of TH and GFAP in VTA and down-regulation of TH and GFAP in NAc to return to the normal leeel. Conclusions： The chronic heroin self administration produced some biochemical adaptations in the related brain regions of the mesolimbic dopamine system and electroacupuncture could promote the repair of the ＂injured＂ DA neurons in VTA of heroin addicted rats and their functional recovery.

关键词： Heroin Dependence Electroacupuncture Substance Withdrawal Syndrome Glial Fibrillary ,acidic Proton tyrosine hydroxylase

Effect of α-synuclein on the promoter activity of tyrosine hydroxylase gene

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Neuroscience Bulletin 2007年第1期23卷 53-57页

作者：高楠李尧华李昕于顺傅桂莲陈彪首都医科大学宣武医院北京老年医学研究所北华大学医学院分子生物学教研室吉林市132013

Objective To approach the associated mechanism by which α-synuclein （α-Syn） might regulate the metabolism of dopamine. Methods A DNA fragment, located at --495 to ＋25 of the human tyrosine hydroxylase （TH） gene, was amplified by PCR and inserted into the pGL3-Basic luciferase reporter vector. The recombinant plasmid pGL3-THprom was transfected into a dopammergic cell line MES23.5 or a α-Syn over-expressed MES23.5 （named MES23.5/hα-Syn^＋）. The promoter activity was detected by the Dual Luciferase Assay System. Results The luciferase activities in the MES23.5 cells transfected with pGl.,3-Basic, pGL3-THprom, and pGL3-Control vectors were 5.60±0.67, 26.80±4.11, and 32.90±4.75, respectively. On the other hand, the luciferase activity of pGL3-THprom in the MES23.5 （26.80±4.11） was significantly higher than that in the MES23.5/hα-Syn^＋（14.40±0.61）（P〈0.01）. Conclusion These results indicate that the -495 to ＋25 region in the TH gene possesses promoter activity for controlling the gene expression, and that α-Syn may negatively regulate the metabolism of dopamine by affecting the function of TH promoter as a trans-acting factor.

关键词： α-synuclein tyrosine hydroxylase gene expression dopamme

Acupuncture Improves Withdrawal Symptoms by Inhibiting tyrosine hydroxylase and Dopamine-beta-hydroxylase Expression in the Midbrain of Heroin Re-addicted Rats

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Acupuncture Improves Withdrawal Symptoms by Inhibiting Tyros...