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Benoît Delignat-Lavaud Charles Ducrot Willemieke Kouwenhoven Nina Feller Louis-ric Trudeau 《Open biology》2022,12(3)
Dopamine (DA) neurons can release DA not just from axon terminals, but also from their somatodendritic (STD) compartment through a mechanism that is still incompletely understood. Using voltammetry in mouse mesencephalic brain slices, we find that STD DA release has low capacity and shows a calcium sensitivity that is comparable to that of axonal release. We find that the molecular mechanism of STD DA release differs from axonal release with regard to the implication of synaptotagmin (Syt) calcium sensors. While individual constitutive knockout of Syt4 or Syt7 is not sufficient to reduce STD DA release, the removal of both isoforms reduces this release by approximately 50%, leaving axonal release unimpaired. Our work unveils clear differences in the mechanisms of STD and axonal DA release. 相似文献
83.
鸣禽的鸣唱与人类的语言产生相似,是一种复杂的习得性行为.因此,鸣禽可以作为研究人类语言学习与产生的重要模式动物.鸣禽鸣唱受到相互联系的鸣唱控制核团调控.多巴胺作为脑内重要的神经递质,参与调控哺乳动物多种活动.多巴胺及其受体在鸣禽鸣唱相关神经核团大量分布.近期研究表明,多巴胺通过调控鸣唱相关核团,促进鸣禽幼年期鸣曲学习、... 相似文献
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Protection of intracellular dopamine cytotoxicity by dopamine disposition and metabolism factors 总被引:2,自引:0,他引:2
Dopamine has been hypothesized as a contributing factor for the selective degeneration of dopaminergic neurons in Parkinson's disease. However, the cytotoxic mechanisms of dopamine and its metabolites remain poorly understood. Using a stable aromatic amino acid decarboxylase (AADC) expressing a fibroblast cell line, we previously demonstrated a novel, non-oxidative cytotoxicity of intracellular dopamine. In this study, we further investigate the roles of dopamine metabolism and disposition proteins against intracellular dopamine cytotoxicity by co-expressing these factors in AADC-expressing cells. Our results indicate that overexpression of the vesicular monoamine transporter and monoamine oxidase A-induced protection against intracellular dopamine toxicity, and conversely that pharmacological inhibition of these pathways potentiated L-DOPA toxicity in catecholaminergic PC12 cells. Macrophage migration inhibitory factor and glutathione S-transferase (GST), factors that have recently been shown to be involved in dopamine metabolism, also exhibited a strong protective role against intracellular dopamine cytotoxicity. Our results support a potential role for non-oxidative cytoplasmic dopamine toxicity, and imply that disruption in dopamine disposition and/or metabolism could underlie the progressive degeneration of dopaminergic neurons in Parkinson's disease. 相似文献
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We have previously described catecholamine-regulated proteins of molecular masses 47, 40 and 26 kDa (CRP47/40/26). In mammals, these proteins are detected only in brain and have been implicated as playing a role in dopaminergic neurotransmission. In this report, we have cloned the cDNA encoding CRP40 from bovine brain. Analysis of the predicted amino acid sequence revealed that the CRP40 product contains an hsp70 motif and shares homology with heat-shock protein hsp70. Immunolocalization studies using mAbs to dopamine show that it colocalizes with CRP40 in the vesicles of dopaminergic neuroblastoma SH-SY5Y cells. The constitutive expression of CRP40 was increased by exposure to heat shock similar to inducible heat-shock protein hsp70 in SH-SY5Y cells. Dopamine significantly modulated the levels of CRP40, whereas, the expression of hsp70 remained unchanged upon dopamine treatment of these cells. Moreover, CRP40 is able to prevent the thermal aggregation of luciferase in vitro, similar to hsp70, suggesting that CRP40 encodes a dopamine-inducible protein with properties similar to heat-shock proteins. The immunofluorescence analyses show that in SH-SY5Y cells, CRP40 translocates to the nucleus during dopamine-induced apoptosis. These results suggest that CRP40 could play a protective role against the harmful effects of catecholamine metabolites. 相似文献
87.
Dulubova I Horiuchi A Snyder GL Girault JA Czernik AJ Shao L Ramabhadran R Greengard P Nairn AC 《Journal of neurochemistry》2001,77(1):229-238
ARPP-16 and ARPP-19 are closely related cAMP-regulated phosphoproteins that were initially discovered in mammalian brain as in vitro substrates for protein kinase A (PKA). ARPP-16 is enriched in dopamine-responsive medium spiny neurons in the striatum, while ARPP-19 is ubiquitously expressed. ARPP-19 is highly homologous to alpha-endosulfine and database searches allowed the identification of novel related proteins in D. melanogaster, C. elegans, S. mansoni and yeast genomes. Using isoform-specific antibodies, we now show that ARPP-19 is composed of at least two differentially expressed isoforms (termed ARPP-19 and ARPP-19e/endosulfine). All ARPP-16/19 family members contain a conserved consensus site for phosphorylation by PKA (RKPSLVA in mammalian ARPP-16 and ARPP-19), and this site was shown to be efficiently phosphorylated in vitro by PKA. An antibody that specifically recognized the phosphorylated form of ARPP-16/19/19e was used to examine the phosphorylation of ARPP-16/19 family members in intact cells. In striatal slices, the phosphorylation of ARPP-16 was increased in response to activation of D(1)-type dopamine receptors, and decreased in response to activation of D(2)-type dopamine receptors. In non-neuronal cells, ARPP-19 was highly phosphorylated in response to activation of PKA. These results establish that ARPP-16/19 proteins constitute a family of PKA-dependent intracellular messengers that function in all cells. The high levels of ARPP-16 in striatal neurons and its bi-directional regulation by dopamine suggest a specific role in dopamine-dependent signal transduction. The conservation of this protein family through evolution suggests that it subserves an important cellular function that is regulated by PKA. 相似文献
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The influence of methamphetamine (METH) on basal ganglia met-enkephalin (Menk) was studied by determining levels of this peptide in striatal, pallidal and nigral regions after administering a single low (0.5 mg/kg) or high (10 mg/kg) dose of this stimulant. The Menk levels in the striatal and pallidal areas were reduced and increased after the low- and high-dose METH treatments, respectively, 12 h after drug administration in all striatal and pallidal regions examined. The low-dose effect appeared to be principally influenced by increased activation of the dopamine D2-like receptor, while the high-dose effect seemed to result from dominance of D1-like receptor activation. However, both effects required coactivation of D1- and D2-like receptors. For the most part, both low- and high-dose METH-induced changes in Menk tissue content were fully recovered by 24 h. The Menk levels were not significantly altered in the substantia nigra 3-24 h after either METH treatment. Results reported herein indicated that striatal and pallidal Menk pathways respond differently after acute treatment with low or high doses of METH. 相似文献