A model of transmembrane helices of dopamine D2 receptor was constructed using the X ray coordinates of bacteriorhodopsin (BR) as a template. Based on the results from the model and the site directed mutagenesis exp...A model of transmembrane helices of dopamine D2 receptor was constructed using the X ray coordinates of bacteriorhodopsin (BR) as a template. Based on the results from the model and the site directed mutagenesis experience, the binding pocket, including nine amino acid residues beside indispensable Asp86, Ser141 and Ser144 residues, was defined. In order to testify the 3D structure of dopamine D2 receptor and specially test the binding sites, two sets of D2 receptor agonists (one was rigid and the other flexible) were selected for docking. A good result of correlation between logIC 50 and binding energy E b indicates that the predicted model is reliable for the investigation of the receptor ligand interaction and design of new active molecules.展开更多
Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus(LEC-DG)are considered responsible for the chronification of pain.However,the underlying alterations in fan cells,whic...Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus(LEC-DG)are considered responsible for the chronification of pain.However,the underlying alterations in fan cells,which are the predominant neurons in the LEC that project to the DG,remain elusive.Here,we investigated possible mechanisms using a rat model of complete Freund’s adjuvant(CFA)-induced inflammatory pain.We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents(Ih),which led to the hyperexcitability of LEC fan cells of CFA slices.This phenomenon was attenuated in CFA slices by activating dopamine D2,but not D1,receptors.Chemogenetic activation of the ventral tegmental area-LEC projection had a D2 receptor-dependent analgesic effect.Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity,and this effect was attenuated by pre-activation of the Ih.Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.展开更多
17β-estradiol modulates the activity of D2 receptors in the regulation of food intake and body weight. The functional lack of 17β-estradiol in postmenopausal women could create a dietary imbalance and cause body wei...17β-estradiol modulates the activity of D2 receptors in the regulation of food intake and body weight. The functional lack of 17β-estradiol in postmenopausal women could create a dietary imbalance and cause body weight gain. This study aimed to better understand the interferences that could exist between 17β-estradiol, D2 receptors and the selection of carbohydrate, fat and protein consumption, as well as their consequences on body weight gain by using an animal model of the menopause. Ovariectomy exacerbates the consumption of foods rich in lipids. Thus confirming an inhibitory action of 17β-estradiol (E2) on the consumption of these types of foods. This consumption stimulates body weight gain, which is promoted by the high caloric content of these foods and not by the amount consumed. Our results showed a direct involvement of D2 receptors in food choice. This choice would be made according to the two (2) isoforms of the D2 receptors. The D2/BR isoform directs towards a high carbohydrate consumption, without causing a gain in body weight. While D2/SUL, promotes high fat food consumption, causing an increase in body weight. In women, 17β-estradiol modulates the activity ratio between these two D2 receptor isoforms to ensure energy and homeostatic balance, stabilizing food intake and body weight.展开更多
Background: Mechanisms underlying overeating-induced obesity in post-menopausal woman include functional lack of 17β-estradiol dysregulating dopamine D2 receptors, thereby inducing food addiction, glucose craving or ...Background: Mechanisms underlying overeating-induced obesity in post-menopausal woman include functional lack of 17β-estradiol dysregulating dopamine D2 receptors, thereby inducing food addiction, glucose craving or alcohol dependence through reward circuitry. This study aimed at further understanding 17β-estradiol and dopamine D2 receptors interferences in the etiology of woman obesity. Method: Seventy-two Wistar female rats weighing 200 - 205 g, individually-housed, were divided into non-ovariectomized control (C = 6 groups) and ovariectomized rats (OVX = 6 groups) which were concurrently subjected to the following treatments: Non-drug-treated (DMSO vehicle), 17β-estradiol (E2, 5 μg/kg, s.c.), sulpiride (SUL, 20 mg/kg, i.p.), bromocriptine (BR, 0.1 mg/kg, i.p.), E2 + SUL or E2 + BR, designating the 6 constitutive groups of either control or ovariectomy. Within each experimental group, consumption of different solutions (10% alcohol, 10% sucrose and water) as well as food intake and body weight were daily measured, for 10 consecutive days. Results: This study indicated that D2S was a specific inducer of alcohol and food intakes, but reduced sugar consumption. In addition, 17β- estradiol regulated the body weight set point, modulating D2S functions towards increased food intake at lower weights and decreased food intake at higher weights. D2S met the slow genomic actions induced by 17β-estradiol. Conversely, D2L inhibited alcohol and food intakes, but induced specifically sugar consumption, thereby regulating blood glucose levels and promoting energy expenditure in reducing body weight. Indeed, 17β-estradiol exerted a tonic inhibition on D2L which was released by OVX, exacerbating sugar intake and increasing body weight. D2L mediated the rapid metabolic effects of 17β-estradiol. Conclusion: Our results supported physiological data reporting that activation of the mostly expressed presynaptically D2S-class autoreceptors decreased dopamine release stimulating food intake, whereas activation of the predominantly postsynaptic isoform D2L receptors increased dopamine activity inhibiting food intake. Our studies indicated that 17β-estradiol acted on the two types of D2 receptors showing opposite functions to equilibrate energy intake vs. expenditure for weight set point regulation. Our data also supported biochemical findings reporting that 17β-estradiol induced D2 genes transcriptional regulation, thereby involving both types of D2 receptors in the etiology of obesity. The combined dysregulated effects of D2L and D2S receptors, as 17β-estradiol was lacking, would be causal factors underlying the etiology of obesity.展开更多
OBJECTIVE Cognitive inflexibility plays a critical role in the compulsive drug taking,a central characteristic of drug addictions,yet its underlying neurochemical mechanisms are not well understood.The present study e...OBJECTIVE Cognitive inflexibility plays a critical role in the compulsive drug taking,a central characteristic of drug addictions,yet its underlying neurochemical mechanisms are not well understood.The present study examined the impact of morphine withdrawal on reversal learning.METHODS Reversal learning was tested in a four-choices digging task.Some brain tissues were harvested 2 h after the behavioral experiment for the further measurement.RESULTS We found that after long-term abstinence for a month from chronic morphine exposure,mice exhibited a profound reversal learning deficit.We further found that dopamine D2 receptor(D2R)system in the frontal-striatal circuit is significantly down-regulated,at both receptor and downstream signals levels.Subsequent pharmacological experiments demonstrated that aripiprazole,a D2R partial agonist,prevented the D2R downregulation and rescued the reversal learning deficit.CONCLUSION Together,our findings provide valuable insights into the causal relationship between D2R system in the frontal-striatal circuit and the cognitive inflexibility caused by abused drugs and offer a promising possibility of an effective therapeutic intervention for drug addictions.展开更多
Our previous studies showed that 17β-estradiol (E2) modulated dopamine D2 receptor in regulating body weight set-point. The aim of this study was to understand whether thiamine deficiency influenced the E2 modulation...Our previous studies showed that 17β-estradiol (E2) modulated dopamine D2 receptor in regulating body weight set-point. The aim of this study was to understand whether thiamine deficiency influenced the E2 modulation on dopamine D2 receptors, using bromocriptine mesylate (BR) and sulpiride (SUL) as selective central dopamine-D2 receptors agonist and antagonist respectively. We studied the E2-dopamine D2 receptors interferences in a 10-day thiamine-deficient female rats for which consumptions of water, sugar, alcohol and food were daily-recorded and their consequences on body weights assessed. Our results showed that the volume of water daily ingested doubled in thiamine-deficient female rats (OXT), while sugar and alcohol consumptions collapsed with decreased weight and food consumption. On the one hand, thiamine potentiated D2/BR activity (bromocriptine-activated D2 receptors) to induce sugar intake and inhibited the same D2/BR receptors to induce water intake. On the other hand, thiamine promoted D2/SUL receptors (sulpiride-inhibited D2 receptors) for enhanced alcohol intake, increased food consumption and weight gain. Taking together, thiamine modulated the actions of 17β-estradiol on both D2/BR and D2/SUL receptors activities.展开更多
GUoblastoma multiforme （GBM） is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent stud- ies indicate that glioma-initiating ceUs/gUoma stem ceils （GICs/GSCs） may be responsibl...GUoblastoma multiforme （GBM） is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent stud- ies indicate that glioma-initiating ceUs/gUoma stem ceils （GICs/GSCs） may be responsible for tumor initiation, infiltration, and recurrence. GICs could aberrantly employ molecular machinery balancing self-renewal and differentiation of embryonic neural precursors. Here, we find that paired related homeobox 1 （PRRX1）, a homeodomain transcription factor that was previously reported to control skeletal development, is expressed in cortical neural progenitors and is required for their self-renewal and proper differentiation. Further, PRRX1 is overrepresented in gUoma samples and labels GlCs. Gtioma celts and GlCs depleted with PRRX1 could not propagate in vitro or form tumors in the xenograft mouse model. The GIC self-renewal function regulated by PRRX1 is mediated by dopamine D2 receptor （DRD2）. PRRX1 directly binds to the DRD2 promoter and transactivates its expression in GICs. Blockage of the DRD2 signaling hampers GIC self-renewal, whereas its overexpression restores the propagating and tumorigenic potential of PRRXl-depleted GlCs. Finally, PRRX1 potentiates GICs via DRD2-mediated extracetlutar signal-related kinase （ERK） and AKT activation. Thus, our study suggests that therapeutic targeting the PRRX1-DRD2-ERK/AKT axis in GICs is a promising strategy for treating GBMs.展开更多
Objective： The aim of this study was to explore the association of dopamine receptor D2 （DRD2） polymorphism and alleviation of obesity in children and adolescents after 8-year follow-up. Methods： This retrospectiv...Objective： The aim of this study was to explore the association of dopamine receptor D2 （DRD2） polymorphism and alleviation of obesity in children and adolescents after 8-year follow-up. Methods： This retrospective cohort study included obese children and adolescents with a follow-up period of 8 years. Baseline clinical character- istics and DRD2 polymorphisms （including rs1076562, rs2075654, and rs4586205） were extracted from medical records. A follow-up visit was performed in May 2017 to collect related data including height, weight, diet compliance, and exercise compliance. Results： One hundred and nine obese children and adolescents were included in the current study. Among three DRD2 single nucleotide polymorphisms, only rs2075654 had a statistically significant association with alleviation of obesity, as the alleviation rate for minor allele carders （68.6% for TC＋TT） was higher compared to the major allele homozygote （43.3% for CC）. After adjusting for all related factors, the hazard ratio of rs2075654 minor allele carders for the alleviation of obesity was 3.34 （95% confidence interval （CI）： 1.30-8.58）. Conclusions： The rs2075654 ~olvmomhism of DRD2 is related to Ionq-term obesity alleviation in obese Chinese children and adolescents.展开更多
Objective： The aim of the study was to observe the effect of total isoflavones from pueraria Iobata （TIP） on D2 dopamine receptor mRNA, preproenkephalin mRNA and prodynorphin mRNA expressions in Parkinson＇s disea...Objective： The aim of the study was to observe the effect of total isoflavones from pueraria Iobata （TIP） on D2 dopamine receptor mRNA, preproenkephalin mRNA and prodynorphin mRNA expressions in Parkinson＇s disease （PD） model cells induced by 1-methyl-4-phenylpyridinium ion （MPP^＋）. Methods： TIP was dissolved in 0.1 M NaOH and added to the culture medium at a final concentrations of 50 mg/L, 100 mg/L and 200 mg/L. Some cells （control） were exposed to 0.001 M NaOH. TIP was added to PC12 cells 30 min prior to the administration of MPP^＋. TIP and MPP^＋ remained in the culture medium for 96 h. D2 dopamine receptor mRNA, preproenkephalin mRNA and prodynorphin mRNA expressions were assayed by real-time quantitative reverse transcription-PCR. Results： The D2 dopamine receptor mRNA and preproenkephalin mRNA expressions were up-regulated in MPP^＋ group compared with the control group, and prodynorphin mRNA expression was down-regulated in that. The D2 dopamine receptor mRNA expression being down-regulated and prodynorphin mRNA expression being up-regulated in TIP group compared with the MPP^＋ group. And there was no effect of TIP on preproenkephalin gene expression in PC12 cells induced by MPP^＋. Conclusion： The results suggest that TIP down-regulates the D2 dopamine receptor mRNA expression, up-regulates prodynorphin mRNA expression and not affects preproenkephalin gene expression in PC12 cells induced by MPP^＋.展开更多
目的考察原儿茶酸对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)致帕金森病(PD)小鼠中脑和纹状体多巴胺D2受体(D2DR)、诱导型一氧化氮合酶(i NOS)和酪氨酸羟化酶(TH)表达的影响。方法选用C57BL褐鼠为实验动物,连续7 d ip MPTP(25 mg/kg)制备P...目的考察原儿茶酸对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)致帕金森病(PD)小鼠中脑和纹状体多巴胺D2受体(D2DR)、诱导型一氧化氮合酶(i NOS)和酪氨酸羟化酶(TH)表达的影响。方法选用C57BL褐鼠为实验动物,连续7 d ip MPTP(25 mg/kg)制备PD动物模型。造模前后分别ip给予原儿茶酸(10 mg/kg)或阳性对照药美多芭(125 mg/kg)进行预防和治疗。应用Western blotting的方法,观察原儿茶酸对PD模型小鼠中脑和纹状体内D2DR、i NOS和TH表达的影响。结果 PD模型小鼠脑组织内i NOS表达升高,D2DR和TH表达下降,而原儿茶酸能够显著降低PD模型小鼠脑中i NOS的表达,提高D2DR和TH的表达量。结论原儿茶酸对MPTP诱导的PD模型小鼠有保护作用,可能通过提高PD模型小鼠中脑和纹状体内D2DR和TH的表达,降低i NOS的表达发挥作用。展开更多
文摘A model of transmembrane helices of dopamine D2 receptor was constructed using the X ray coordinates of bacteriorhodopsin (BR) as a template. Based on the results from the model and the site directed mutagenesis experience, the binding pocket, including nine amino acid residues beside indispensable Asp86, Ser141 and Ser144 residues, was defined. In order to testify the 3D structure of dopamine D2 receptor and specially test the binding sites, two sets of D2 receptor agonists (one was rigid and the other flexible) were selected for docking. A good result of correlation between logIC 50 and binding energy E b indicates that the predicted model is reliable for the investigation of the receptor ligand interaction and design of new active molecules.
基金supported by the National Natural Science Foundation of China(81901119 and 81901142)Special Project on Innovation and Generation of Medical Support Capacity,and the Natural Science Foundation of Tibet(XZ2019ZRG-119),China.
文摘Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus(LEC-DG)are considered responsible for the chronification of pain.However,the underlying alterations in fan cells,which are the predominant neurons in the LEC that project to the DG,remain elusive.Here,we investigated possible mechanisms using a rat model of complete Freund’s adjuvant(CFA)-induced inflammatory pain.We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents(Ih),which led to the hyperexcitability of LEC fan cells of CFA slices.This phenomenon was attenuated in CFA slices by activating dopamine D2,but not D1,receptors.Chemogenetic activation of the ventral tegmental area-LEC projection had a D2 receptor-dependent analgesic effect.Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity,and this effect was attenuated by pre-activation of the Ih.Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.
文摘17β-estradiol modulates the activity of D2 receptors in the regulation of food intake and body weight. The functional lack of 17β-estradiol in postmenopausal women could create a dietary imbalance and cause body weight gain. This study aimed to better understand the interferences that could exist between 17β-estradiol, D2 receptors and the selection of carbohydrate, fat and protein consumption, as well as their consequences on body weight gain by using an animal model of the menopause. Ovariectomy exacerbates the consumption of foods rich in lipids. Thus confirming an inhibitory action of 17β-estradiol (E2) on the consumption of these types of foods. This consumption stimulates body weight gain, which is promoted by the high caloric content of these foods and not by the amount consumed. Our results showed a direct involvement of D2 receptors in food choice. This choice would be made according to the two (2) isoforms of the D2 receptors. The D2/BR isoform directs towards a high carbohydrate consumption, without causing a gain in body weight. While D2/SUL, promotes high fat food consumption, causing an increase in body weight. In women, 17β-estradiol modulates the activity ratio between these two D2 receptor isoforms to ensure energy and homeostatic balance, stabilizing food intake and body weight.
文摘Background: Mechanisms underlying overeating-induced obesity in post-menopausal woman include functional lack of 17β-estradiol dysregulating dopamine D2 receptors, thereby inducing food addiction, glucose craving or alcohol dependence through reward circuitry. This study aimed at further understanding 17β-estradiol and dopamine D2 receptors interferences in the etiology of woman obesity. Method: Seventy-two Wistar female rats weighing 200 - 205 g, individually-housed, were divided into non-ovariectomized control (C = 6 groups) and ovariectomized rats (OVX = 6 groups) which were concurrently subjected to the following treatments: Non-drug-treated (DMSO vehicle), 17β-estradiol (E2, 5 μg/kg, s.c.), sulpiride (SUL, 20 mg/kg, i.p.), bromocriptine (BR, 0.1 mg/kg, i.p.), E2 + SUL or E2 + BR, designating the 6 constitutive groups of either control or ovariectomy. Within each experimental group, consumption of different solutions (10% alcohol, 10% sucrose and water) as well as food intake and body weight were daily measured, for 10 consecutive days. Results: This study indicated that D2S was a specific inducer of alcohol and food intakes, but reduced sugar consumption. In addition, 17β- estradiol regulated the body weight set point, modulating D2S functions towards increased food intake at lower weights and decreased food intake at higher weights. D2S met the slow genomic actions induced by 17β-estradiol. Conversely, D2L inhibited alcohol and food intakes, but induced specifically sugar consumption, thereby regulating blood glucose levels and promoting energy expenditure in reducing body weight. Indeed, 17β-estradiol exerted a tonic inhibition on D2L which was released by OVX, exacerbating sugar intake and increasing body weight. D2L mediated the rapid metabolic effects of 17β-estradiol. Conclusion: Our results supported physiological data reporting that activation of the mostly expressed presynaptically D2S-class autoreceptors decreased dopamine release stimulating food intake, whereas activation of the predominantly postsynaptic isoform D2L receptors increased dopamine activity inhibiting food intake. Our studies indicated that 17β-estradiol acted on the two types of D2 receptors showing opposite functions to equilibrate energy intake vs. expenditure for weight set point regulation. Our data also supported biochemical findings reporting that 17β-estradiol induced D2 genes transcriptional regulation, thereby involving both types of D2 receptors in the etiology of obesity. The combined dysregulated effects of D2L and D2S receptors, as 17β-estradiol was lacking, would be causal factors underlying the etiology of obesity.
文摘OBJECTIVE Cognitive inflexibility plays a critical role in the compulsive drug taking,a central characteristic of drug addictions,yet its underlying neurochemical mechanisms are not well understood.The present study examined the impact of morphine withdrawal on reversal learning.METHODS Reversal learning was tested in a four-choices digging task.Some brain tissues were harvested 2 h after the behavioral experiment for the further measurement.RESULTS We found that after long-term abstinence for a month from chronic morphine exposure,mice exhibited a profound reversal learning deficit.We further found that dopamine D2 receptor(D2R)system in the frontal-striatal circuit is significantly down-regulated,at both receptor and downstream signals levels.Subsequent pharmacological experiments demonstrated that aripiprazole,a D2R partial agonist,prevented the D2R downregulation and rescued the reversal learning deficit.CONCLUSION Together,our findings provide valuable insights into the causal relationship between D2R system in the frontal-striatal circuit and the cognitive inflexibility caused by abused drugs and offer a promising possibility of an effective therapeutic intervention for drug addictions.
文摘Our previous studies showed that 17β-estradiol (E2) modulated dopamine D2 receptor in regulating body weight set-point. The aim of this study was to understand whether thiamine deficiency influenced the E2 modulation on dopamine D2 receptors, using bromocriptine mesylate (BR) and sulpiride (SUL) as selective central dopamine-D2 receptors agonist and antagonist respectively. We studied the E2-dopamine D2 receptors interferences in a 10-day thiamine-deficient female rats for which consumptions of water, sugar, alcohol and food were daily-recorded and their consequences on body weights assessed. Our results showed that the volume of water daily ingested doubled in thiamine-deficient female rats (OXT), while sugar and alcohol consumptions collapsed with decreased weight and food consumption. On the one hand, thiamine potentiated D2/BR activity (bromocriptine-activated D2 receptors) to induce sugar intake and inhibited the same D2/BR receptors to induce water intake. On the other hand, thiamine promoted D2/SUL receptors (sulpiride-inhibited D2 receptors) for enhanced alcohol intake, increased food consumption and weight gain. Taking together, thiamine modulated the actions of 17β-estradiol on both D2/BR and D2/SUL receptors activities.
基金This work was supported by grants from the National Natural Science Foundation of China （31671418 and 31471361）, the National Key Basic Research Program of China （2012CB967002）, and Fundamental Research Funds for the Central Universities （2042016kf1020 and 2042017kf0205） to Y.Z. and the NIH grant （HL119478） to 6.D.
文摘GUoblastoma multiforme （GBM） is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent stud- ies indicate that glioma-initiating ceUs/gUoma stem ceils （GICs/GSCs） may be responsible for tumor initiation, infiltration, and recurrence. GICs could aberrantly employ molecular machinery balancing self-renewal and differentiation of embryonic neural precursors. Here, we find that paired related homeobox 1 （PRRX1）, a homeodomain transcription factor that was previously reported to control skeletal development, is expressed in cortical neural progenitors and is required for their self-renewal and proper differentiation. Further, PRRX1 is overrepresented in gUoma samples and labels GlCs. Gtioma celts and GlCs depleted with PRRX1 could not propagate in vitro or form tumors in the xenograft mouse model. The GIC self-renewal function regulated by PRRX1 is mediated by dopamine D2 receptor （DRD2）. PRRX1 directly binds to the DRD2 promoter and transactivates its expression in GICs. Blockage of the DRD2 signaling hampers GIC self-renewal, whereas its overexpression restores the propagating and tumorigenic potential of PRRXl-depleted GlCs. Finally, PRRX1 potentiates GICs via DRD2-mediated extracetlutar signal-related kinase （ERK） and AKT activation. Thus, our study suggests that therapeutic targeting the PRRX1-DRD2-ERK/AKT axis in GICs is a promising strategy for treating GBMs.
基金Project supported by the National Natural Science Foundation of China(No.11571309)the National Key Research and Development Programme of China(No.2016YFC1305301)the Jin Lei Pediatric Endocrinology Growth Research Fund for Young Physicians(No.PEGRF201405001),China
文摘Objective： The aim of this study was to explore the association of dopamine receptor D2 （DRD2） polymorphism and alleviation of obesity in children and adolescents after 8-year follow-up. Methods： This retrospective cohort study included obese children and adolescents with a follow-up period of 8 years. Baseline clinical character- istics and DRD2 polymorphisms （including rs1076562, rs2075654, and rs4586205） were extracted from medical records. A follow-up visit was performed in May 2017 to collect related data including height, weight, diet compliance, and exercise compliance. Results： One hundred and nine obese children and adolescents were included in the current study. Among three DRD2 single nucleotide polymorphisms, only rs2075654 had a statistically significant association with alleviation of obesity, as the alleviation rate for minor allele carders （68.6% for TC＋TT） was higher compared to the major allele homozygote （43.3% for CC）. After adjusting for all related factors, the hazard ratio of rs2075654 minor allele carders for the alleviation of obesity was 3.34 （95% confidence interval （CI）： 1.30-8.58）. Conclusions： The rs2075654 ~olvmomhism of DRD2 is related to Ionq-term obesity alleviation in obese Chinese children and adolescents.
基金Supported by the grants from the National Natural Science Foundation of China (No. 30873396)the National Science Foundation for Postdoctoral Scientists of China (No. 20080430140)+1 种基金Research Foundation of Education Bureau of Heilongjiang Province (No. 11511455)the Qiqihar Foundation for Development of Science and Technology, China(No. SF-08002)
文摘Objective： The aim of the study was to observe the effect of total isoflavones from pueraria Iobata （TIP） on D2 dopamine receptor mRNA, preproenkephalin mRNA and prodynorphin mRNA expressions in Parkinson＇s disease （PD） model cells induced by 1-methyl-4-phenylpyridinium ion （MPP^＋）. Methods： TIP was dissolved in 0.1 M NaOH and added to the culture medium at a final concentrations of 50 mg/L, 100 mg/L and 200 mg/L. Some cells （control） were exposed to 0.001 M NaOH. TIP was added to PC12 cells 30 min prior to the administration of MPP^＋. TIP and MPP^＋ remained in the culture medium for 96 h. D2 dopamine receptor mRNA, preproenkephalin mRNA and prodynorphin mRNA expressions were assayed by real-time quantitative reverse transcription-PCR. Results： The D2 dopamine receptor mRNA and preproenkephalin mRNA expressions were up-regulated in MPP^＋ group compared with the control group, and prodynorphin mRNA expression was down-regulated in that. The D2 dopamine receptor mRNA expression being down-regulated and prodynorphin mRNA expression being up-regulated in TIP group compared with the MPP^＋ group. And there was no effect of TIP on preproenkephalin gene expression in PC12 cells induced by MPP^＋. Conclusion： The results suggest that TIP down-regulates the D2 dopamine receptor mRNA expression, up-regulates prodynorphin mRNA expression and not affects preproenkephalin gene expression in PC12 cells induced by MPP^＋.
