Dogs show high social communicative ability in interactions with humans. We investigated the association between dogs’ social communicative behavior and the polymorphisms of a gene related to a neurotransmitter. We u...Dogs show high social communicative ability in interactions with humans. We investigated the association between dogs’ social communicative behavior and the polymorphisms of a gene related to a neurotransmitter. We used an “unsolvable task”, in which an experimenter put a food reward into a container and closed it firmly so that dogs could not remove the reward. Human-directed gazing, possibly to request help, is a characteristic behavioral trait of dogs in such situations. The association between owner-directed gazing behavior in the unsolvable task and polymorphisms of three regions (exon1, exon3, intron2) in the dopamine receptor D4 gene (DRD4) was analyzed. We found that the genotype of DRD4 intron2 was significantly associated with the dogs’ gazing behavior. Dogs carrying shorter allele (P) looked at their owner more frequently, for longer, and earlier than dogs carrying longer allele (Q). This result suggests that polymorphism in DRD4 intron2 may affect social communication and cognition in dogs.展开更多
Schizophrenia is a disease that affects many areas of the brain. The dopamine hypothesis is one of the most widely-accepted ideas in the pathophysiology of schizophrenia. Besides alterations in the dopaminergic system...Schizophrenia is a disease that affects many areas of the brain. The dopamine hypothesis is one of the most widely-accepted ideas in the pathophysiology of schizophrenia. Besides alterations in the dopaminergic system in the central nervous system, there have been several reports of changes in dopaminergic systems in the peripheral blood of schizophrenic patients. Several reports have shown that dopamine receptor expression by lymphocytes is altered in patients with schizophrenia, but the results have been conflicting. We therefore re-assessed D3R and D4R mRNA levels in 11 patients with schizophrenia and 12 healthy subjects and correlated levels with severity of symptoms. D3R and D4R expression in lymphocytes and granulocytes was measured by quantitative RT-PCR and the severity of symptoms and cognitive impairment were assessed using the PANSS and BACS-J. There were no significant differences in mean D3R or D4R mRNA levels in lymphocytes from schizophrenic patients and controls and no significant difference in mean D4R mRNA levels in granulocytes (D3R mRNA undetectable). In patients with schizophrenia, D3R expression was inversely correlated with the total PANSS score (r = 0.768, p = 0.009), while D4R expression was positively correlated with working memory scales (r = 0.895, p = 0.001). In conclusion, these results imply that lymphocyte D3R and D4R are involved in the mechanisms of the disorder and could be used as target markers in the treatment of schizophrenia.展开更多
OBJECTIVE Abnormal striatal dopaminergic and glutamatergic neurotransmis⁃sion is central to the pathophysiology of schizo⁃phrenia.In this study,we investigated the roles of M4 receptor interplay with D1 signaling in s...OBJECTIVE Abnormal striatal dopaminergic and glutamatergic neurotransmis⁃sion is central to the pathophysiology of schizo⁃phrenia.In this study,we investigated the roles of M4 receptor interplay with D1 signaling in stria⁃tal neurotransmission that affect glutamatergic transmission to control the etiology of neuropsy⁃chiatric disorders.METHODS To study dorsal striatum(DS)region-specific neuronal and behav⁃ioral responses modulated by M4 receptors,we used clustered regularly interspaced short palin⁃dromic repeats-associated protein 9 technology to generate mice lacking M4 in the dorsal stria⁃tum(DS-M4-KD).The M4 positive allosteric modu⁃lator,VU0467154,were used to study the phar⁃macologically profiles with M4 receptor stimula⁃tion in WT mice.Oxotremorine M(Oxo-M),a no subtype-selective muscarinic agonist,was used to show that mAchRs activation,in order to dissect the particular function of M4,in DS-M4-KD mice.Open filed test and forced swim test were used to assess the change of psychiatric-like behav⁃iors.Western blotting and immunohistochemistry were used to detect protein levels of phosphory⁃lation site of dopamine-and cAMP-regulated phosphoprotein of 32 ku(DARPP-32).Whole-cell patch-clamp recording was used to assess M4-mediated cholinergic inhibition of glutamater⁃gic synaptic input transmission.RESULTS West⁃ern blotting and immunohistochemistry assay showed VU0467154(5 mg·kg-1,ip)promoted phosphorylation of DARPP-32 at Thr75,and atten⁃uated D1-dependent phosphorylation of DARPP-32 at Thr34 within the mouse DS.Consistently,the Oxo-M(4μg,icv)also increased DARPP-32 phosphorylation at site Thr75 to reversed phos⁃phorylation at site Thr34 in WT mice,but not in DS-M4-KD mice.In parallel with altered DARPP-32 responses,VU0467154 or Oxo-M evoked a psychological stress response and reversed D1-induced hyperlocomotion in mice in open field test and force swim tests.However,Oxo-M sup⁃pression of D1-depengdeng behavioral respons⁃es was impaired in DS-M4-KD mice.Whole-cell patch recording showed that VU0467154 or Oxo-M mediated endogenous cholinergic inhibition of miniature excitatory postsynaptic currents through M4 receptors,which in turn suppressed D1-depen⁃dent glutamatergic synaptic transmission in the DS.CONCLUSION This study provides evidence for the role of M4 receptors in regulation of dopa⁃mine/DARPP-32 signaling and glutamate respons⁃es in the DS,and therefore modulation of psychi⁃atric behaviors associated with D1 signaling.This results indicate the mechanisms of treatments targeting M4 in psychiatric disorders.展开更多
The major cause of pulmonary vascular remodeling in broilers is abnormal proliferation of vascular smooth muscle cells(VSMCs),and one of the main causes of pulmonary hypertension syndrome(PHS)in broilers is pulmonary ...The major cause of pulmonary vascular remodeling in broilers is abnormal proliferation of vascular smooth muscle cells(VSMCs),and one of the main causes of pulmonary hypertension syndrome(PHS)in broilers is pulmonary artery vascular remodeling.Forty Arbor Acres(AA)broilers were randomly divided into four groups(n=10):a control group(deionized water,Og/L NaCl),a freshwater group(FW,deionized water+1 g/L NaCl),highly salinized freshwater group 1(H-SFW-1,deionized water+2.5 g/L NaCl)and highly salinized freshwater group 2(H-SFW-2,deionized water+5 g/L NaCl).The results of in vivo experiments showed that vascular smooth muscle of the broilers could be significantly proliferated by intake of high-salinity fresh water(H-SFW-1&H-SFW-2),which significantly increased the content of angiotensin II(Ang II)and the expression of angiotensin II type 1(AT1)receptor protein.Meanwhile,it significantly decreased the expression of dopamine receptor D4(DRD4)protein.The results of in vitro experiments showed that exogenous Ang II induced the proliferation of primary VSMCs in broilers,which could be significantly inhibited by DRD4 agonists(D4A,HY-101384A)and enhanced by DRD4 inhibitors(D4I;HY-B0965).In addition,the results of immunoblotting and fluorescence quantitative PCR showed that AT1 receptors could be negatively regulated by DRD4 in VSMCs of broilers,either at the transcriptional or translational level.At the same time,the expression of AT1 receptor could be increased by DRD4 inhibition by D4I and decreased by DRD4 activation by D4A.The negative regulatory effect of DRD4 on AT1 receptor occurred in a dose-dependent manner.These results indicate that long-term intake of highly salinized fresh water can cause PHS in broilers,accompanied by varying degrees of proliferation of pulmonary artery smooth muscle.This mechanism may involve response of its receptor being induced by increased Ang II,while DRD4 can negatively regulate it.展开更多
目的探讨福建省Tourette综合征与DRD4基因第3号外显子48bp VNTR多态性的关系。方法研究对象包括120名正常人和106例Tourette综合征(Gilles de la Tourette syndrom,TS)患者。采用抽提人基因组DNA、聚合酶链反应、琼脂糖凝胶电泳,结合PAG...目的探讨福建省Tourette综合征与DRD4基因第3号外显子48bp VNTR多态性的关系。方法研究对象包括120名正常人和106例Tourette综合征(Gilles de la Tourette syndrom,TS)患者。采用抽提人基因组DNA、聚合酶链反应、琼脂糖凝胶电泳,结合PAGE胶电泳及银染技术检测DRD4基因第3外显子48bpVNTR多态性的等位基因和基因型。部分有代表性等位基因片段的PCR产物直接测序,检测其基因型。将TS患者与正常人的DRD4基因型进行对比,分析其与TS的相关性。结果 TS组与对照组中,DRD448bpVNTR共检测到8种基因型,有5种等位基因,即对应2～6次重复。DRD448bpVNTR基因型总体分布趋势、DRD4等位基因频率分布、DRD448bpVNTR长短重复等位基因比较,TS组与对照组差异有统计学意义(P<0.05)。结论 DRD4第3号外显子的48bpVNTR多态性可能与福建省TS有关联。展开更多
Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mic...Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mice were used to examine the lineage differentiation of SOX2-positive cells during the development of cerebral cortex.Primary NSCs/astrocytes culture,ChIP-seq and Western Blot were adopted to analyze and verify the expression of candidate genes.Pharmacological manipulation,neurosphere formation,photochemical ischemia,immunofluorescence staining and behavior tests were adopted to evaluate the effects of activating DRD2 signaling on astrocytic dedifferentiation.Results:Immunofluorescence staining demonstrated the NSC-astrocyte switch of SOX2-expression in the normal development of cerebral cortex.ChIP-seq revealed enrichment of DRD2 signaling by SOX2-bound enhancers in NSCs and SOX2-bound promoters in astrocytes.Western Blot and immunofluorescence staining verified the expression of DRD2 in NSCs and reactive astrocytes.Application of quinagolide hydrocholoride(QH),an agonist of DRD2,significantly promoted astrocytic dedifferentiation both in vitro and in vivo following ischemia.In addition,quinagolide hydrocholoride treatment improved locomotion recovery.Conclusion:Activating DRD2 signaling facilitates astrocytic dedifferentiation and may be used to treat ischemic stroke.展开更多
Background: Recent studies indicate that C-X-C motif chemokine receptor 4(CXCR4) and its ligand, C-X-C motif chemokine ligand 12(CXCL12), stimulate expression of the cell cycle regulatory protein Cyclin D1 in neurofib...Background: Recent studies indicate that C-X-C motif chemokine receptor 4(CXCR4) and its ligand, C-X-C motif chemokine ligand 12(CXCL12), stimulate expression of the cell cycle regulatory protein Cyclin D1 in neurofibromatosis 1-associated malignant peripheral nerve sheath tumor(MPNST) cells and promote their proliferation. In this study, we measured the expression of CXCR4, CXCL12, and Cyclin D1 proteins in sporadic MPNST tissues from Chinese patients and investigated their prognostic values.Methods: CXCR4, CXCL12, and Cyclin D1 protein expression in samples from 58 Chinese patients with sporadic MPNST was assessed with immunohistochemical staining.Their prognostic values were evaluated with Kaplan-Meier analysis and a log-rank test. Multivariate Cox regression analysis was used to identify independent prognostic factors.Results: High expression of CXCR4, CXCL12, and Cyclin D1 was observed in 19(32.8%), 32(55.2%), and 16(27.6%)samples, respectively. CXCR4 expression was positively correlated with CXCL12 expression(r = 0.334, P = 0.010) and Cyclin D1 expression(r = 0.309, P = 0.018). Patients with high CXCR4 expression showed longer overall survival than those with low CXCR4 expression(χ~2 = 4.642, P = 0.031).Conclusion: High CXCR4 expression may define a specific subtype of sporadic MPNST with favorable prognosis.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
文摘Dogs show high social communicative ability in interactions with humans. We investigated the association between dogs’ social communicative behavior and the polymorphisms of a gene related to a neurotransmitter. We used an “unsolvable task”, in which an experimenter put a food reward into a container and closed it firmly so that dogs could not remove the reward. Human-directed gazing, possibly to request help, is a characteristic behavioral trait of dogs in such situations. The association between owner-directed gazing behavior in the unsolvable task and polymorphisms of three regions (exon1, exon3, intron2) in the dopamine receptor D4 gene (DRD4) was analyzed. We found that the genotype of DRD4 intron2 was significantly associated with the dogs’ gazing behavior. Dogs carrying shorter allele (P) looked at their owner more frequently, for longer, and earlier than dogs carrying longer allele (Q). This result suggests that polymorphism in DRD4 intron2 may affect social communication and cognition in dogs.
文摘Schizophrenia is a disease that affects many areas of the brain. The dopamine hypothesis is one of the most widely-accepted ideas in the pathophysiology of schizophrenia. Besides alterations in the dopaminergic system in the central nervous system, there have been several reports of changes in dopaminergic systems in the peripheral blood of schizophrenic patients. Several reports have shown that dopamine receptor expression by lymphocytes is altered in patients with schizophrenia, but the results have been conflicting. We therefore re-assessed D3R and D4R mRNA levels in 11 patients with schizophrenia and 12 healthy subjects and correlated levels with severity of symptoms. D3R and D4R expression in lymphocytes and granulocytes was measured by quantitative RT-PCR and the severity of symptoms and cognitive impairment were assessed using the PANSS and BACS-J. There were no significant differences in mean D3R or D4R mRNA levels in lymphocytes from schizophrenic patients and controls and no significant difference in mean D4R mRNA levels in granulocytes (D3R mRNA undetectable). In patients with schizophrenia, D3R expression was inversely correlated with the total PANSS score (r = 0.768, p = 0.009), while D4R expression was positively correlated with working memory scales (r = 0.895, p = 0.001). In conclusion, these results imply that lymphocyte D3R and D4R are involved in the mechanisms of the disorder and could be used as target markers in the treatment of schizophrenia.
文摘OBJECTIVE Abnormal striatal dopaminergic and glutamatergic neurotransmis⁃sion is central to the pathophysiology of schizo⁃phrenia.In this study,we investigated the roles of M4 receptor interplay with D1 signaling in stria⁃tal neurotransmission that affect glutamatergic transmission to control the etiology of neuropsy⁃chiatric disorders.METHODS To study dorsal striatum(DS)region-specific neuronal and behav⁃ioral responses modulated by M4 receptors,we used clustered regularly interspaced short palin⁃dromic repeats-associated protein 9 technology to generate mice lacking M4 in the dorsal stria⁃tum(DS-M4-KD).The M4 positive allosteric modu⁃lator,VU0467154,were used to study the phar⁃macologically profiles with M4 receptor stimula⁃tion in WT mice.Oxotremorine M(Oxo-M),a no subtype-selective muscarinic agonist,was used to show that mAchRs activation,in order to dissect the particular function of M4,in DS-M4-KD mice.Open filed test and forced swim test were used to assess the change of psychiatric-like behav⁃iors.Western blotting and immunohistochemistry were used to detect protein levels of phosphory⁃lation site of dopamine-and cAMP-regulated phosphoprotein of 32 ku(DARPP-32).Whole-cell patch-clamp recording was used to assess M4-mediated cholinergic inhibition of glutamater⁃gic synaptic input transmission.RESULTS West⁃ern blotting and immunohistochemistry assay showed VU0467154(5 mg·kg-1,ip)promoted phosphorylation of DARPP-32 at Thr75,and atten⁃uated D1-dependent phosphorylation of DARPP-32 at Thr34 within the mouse DS.Consistently,the Oxo-M(4μg,icv)also increased DARPP-32 phosphorylation at site Thr75 to reversed phos⁃phorylation at site Thr34 in WT mice,but not in DS-M4-KD mice.In parallel with altered DARPP-32 responses,VU0467154 or Oxo-M evoked a psychological stress response and reversed D1-induced hyperlocomotion in mice in open field test and force swim tests.However,Oxo-M sup⁃pression of D1-depengdeng behavioral respons⁃es was impaired in DS-M4-KD mice.Whole-cell patch recording showed that VU0467154 or Oxo-M mediated endogenous cholinergic inhibition of miniature excitatory postsynaptic currents through M4 receptors,which in turn suppressed D1-depen⁃dent glutamatergic synaptic transmission in the DS.CONCLUSION This study provides evidence for the role of M4 receptors in regulation of dopa⁃mine/DARPP-32 signaling and glutamate respons⁃es in the DS,and therefore modulation of psychi⁃atric behaviors associated with D1 signaling.This results indicate the mechanisms of treatments targeting M4 in psychiatric disorders.
基金This research was funded by the Fundamental Research Funds for the Central Universities(Grant No.2662020DKPY013)the National Natural Science Foundation of China(Grant No.31972748)the Huazhong Agricultural University 2020 College Student Science and Technology Innovation Fund(SRF).
文摘The major cause of pulmonary vascular remodeling in broilers is abnormal proliferation of vascular smooth muscle cells(VSMCs),and one of the main causes of pulmonary hypertension syndrome(PHS)in broilers is pulmonary artery vascular remodeling.Forty Arbor Acres(AA)broilers were randomly divided into four groups(n=10):a control group(deionized water,Og/L NaCl),a freshwater group(FW,deionized water+1 g/L NaCl),highly salinized freshwater group 1(H-SFW-1,deionized water+2.5 g/L NaCl)and highly salinized freshwater group 2(H-SFW-2,deionized water+5 g/L NaCl).The results of in vivo experiments showed that vascular smooth muscle of the broilers could be significantly proliferated by intake of high-salinity fresh water(H-SFW-1&H-SFW-2),which significantly increased the content of angiotensin II(Ang II)and the expression of angiotensin II type 1(AT1)receptor protein.Meanwhile,it significantly decreased the expression of dopamine receptor D4(DRD4)protein.The results of in vitro experiments showed that exogenous Ang II induced the proliferation of primary VSMCs in broilers,which could be significantly inhibited by DRD4 agonists(D4A,HY-101384A)and enhanced by DRD4 inhibitors(D4I;HY-B0965).In addition,the results of immunoblotting and fluorescence quantitative PCR showed that AT1 receptors could be negatively regulated by DRD4 in VSMCs of broilers,either at the transcriptional or translational level.At the same time,the expression of AT1 receptor could be increased by DRD4 inhibition by D4I and decreased by DRD4 activation by D4A.The negative regulatory effect of DRD4 on AT1 receptor occurred in a dose-dependent manner.These results indicate that long-term intake of highly salinized fresh water can cause PHS in broilers,accompanied by varying degrees of proliferation of pulmonary artery smooth muscle.This mechanism may involve response of its receptor being induced by increased Ang II,while DRD4 can negatively regulate it.
文摘目的探讨福建省Tourette综合征与DRD4基因第3号外显子48bp VNTR多态性的关系。方法研究对象包括120名正常人和106例Tourette综合征(Gilles de la Tourette syndrom,TS)患者。采用抽提人基因组DNA、聚合酶链反应、琼脂糖凝胶电泳,结合PAGE胶电泳及银染技术检测DRD4基因第3外显子48bpVNTR多态性的等位基因和基因型。部分有代表性等位基因片段的PCR产物直接测序,检测其基因型。将TS患者与正常人的DRD4基因型进行对比,分析其与TS的相关性。结果 TS组与对照组中,DRD448bpVNTR共检测到8种基因型,有5种等位基因,即对应2～6次重复。DRD448bpVNTR基因型总体分布趋势、DRD4等位基因频率分布、DRD448bpVNTR长短重复等位基因比较,TS组与对照组差异有统计学意义(P<0.05)。结论 DRD4第3号外显子的48bpVNTR多态性可能与福建省TS有关联。
文摘Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mice were used to examine the lineage differentiation of SOX2-positive cells during the development of cerebral cortex.Primary NSCs/astrocytes culture,ChIP-seq and Western Blot were adopted to analyze and verify the expression of candidate genes.Pharmacological manipulation,neurosphere formation,photochemical ischemia,immunofluorescence staining and behavior tests were adopted to evaluate the effects of activating DRD2 signaling on astrocytic dedifferentiation.Results:Immunofluorescence staining demonstrated the NSC-astrocyte switch of SOX2-expression in the normal development of cerebral cortex.ChIP-seq revealed enrichment of DRD2 signaling by SOX2-bound enhancers in NSCs and SOX2-bound promoters in astrocytes.Western Blot and immunofluorescence staining verified the expression of DRD2 in NSCs and reactive astrocytes.Application of quinagolide hydrocholoride(QH),an agonist of DRD2,significantly promoted astrocytic dedifferentiation both in vitro and in vivo following ischemia.In addition,quinagolide hydrocholoride treatment improved locomotion recovery.Conclusion:Activating DRD2 signaling facilitates astrocytic dedifferentiation and may be used to treat ischemic stroke.
基金supported by the National Nature Science Foundation of China(81372872 to Jilong Yang,81672650 to Ze Zhu,and 81402215 to Xiaoling Du)funds from the University Cancer Foundation via the Sister Institution Network Fund(to Jilong Yang)
文摘Background: Recent studies indicate that C-X-C motif chemokine receptor 4(CXCR4) and its ligand, C-X-C motif chemokine ligand 12(CXCL12), stimulate expression of the cell cycle regulatory protein Cyclin D1 in neurofibromatosis 1-associated malignant peripheral nerve sheath tumor(MPNST) cells and promote their proliferation. In this study, we measured the expression of CXCR4, CXCL12, and Cyclin D1 proteins in sporadic MPNST tissues from Chinese patients and investigated their prognostic values.Methods: CXCR4, CXCL12, and Cyclin D1 protein expression in samples from 58 Chinese patients with sporadic MPNST was assessed with immunohistochemical staining.Their prognostic values were evaluated with Kaplan-Meier analysis and a log-rank test. Multivariate Cox regression analysis was used to identify independent prognostic factors.Results: High expression of CXCR4, CXCL12, and Cyclin D1 was observed in 19(32.8%), 32(55.2%), and 16(27.6%)samples, respectively. CXCR4 expression was positively correlated with CXCL12 expression(r = 0.334, P = 0.010) and Cyclin D1 expression(r = 0.309, P = 0.018). Patients with high CXCR4 expression showed longer overall survival than those with low CXCR4 expression(χ~2 = 4.642, P = 0.031).Conclusion: High CXCR4 expression may define a specific subtype of sporadic MPNST with favorable prognosis.
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^＋.
