Dietary curcumin supplementation attenuates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in C57BL mice

Studies in vivo and in vitro suggest that curcumin is a neuroprotective agent. Experiments were conducted to determine whether dietary supplementation with curcumin has neuroprotective effects in a mouse model of Parkinson’s disease (PD). Treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) significantly induced the loss of dopaminergic cells in the substantia nigra and deletion of dopamine in the striatum, which was attenuated by long-term (7 weeks) dietary supplementation with curcumin at a concentration of 0.5% or 2.0% (w/w). Although curcumin did not prevent the MPTP-induced apoptosis of neuroblasts in the subventricular zone (SVZ), it promoted the regeneration of neuroblasts in the anterior part of the SVZ (SVZa) at 3 days after MPTP treatment. Furthermore, curcumin enhanced the MPTP-induced activation of microglia and astrocytes in the striatum and increased the expression of glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-β1 (TGFβ1) in the striatum and SVZ. GDNF and TGFβ1 are thought to play an important role in protecting neurons from injury in the central and peripheral nervous systems. These results suggest that long-term administration of curcumin blocks the neurotoxicity of MPTP in the nigrostriatal dopaminergic system of the mouse and that the neuroprotective effect might be correlated with the increased expression of GDNF and TGFβ1. Curcumin may be effective in preventing or slowing the progression of PD.     

Hypothalamic dopamine is required for salsolinol‐induced prolactin secretion in goats

The aim of the present study was to clarify the relationship between hypothalamic dopamine (DA) and salsolinol (SAL) for the secretion of prolactin (PRL) in goats. SAL or thyrotropin‐releasing hormone (TRH) was intravenously injected into female goats treated with or without the D₂ DA receptor antagonist haloperidol (Hal), which crosses the blood‐brain barrier, and the PRL‐releasing response to SAL was compared with that to TRH. PRL‐releasing responses to SAL, Hal, and Hal plus SAL were also examined after a pretreatment to augment central DA using carbidopa (Carbi) and L‐dopa. The PRL‐releasing response to Hal alone was greater than that to SAL or TRH alone. The PRL‐releasing response to Hal plus SAL was similar to that of Hal alone. In contrast, the PRL‐releasing response to Hal plus TRH was greater than that to TRH or Hal alone. The treatment with Carbi plus L‐dopa inhibited SAL‐ and Hal‐induced PRL secretion. The inhibition of the PRL‐releasing response to SAL disappeared when SAL was injected with Hal. These results indicate that the mechanisms underlying the SAL‐induced PRL response differ from those of TRH, and suggest that hypothalamic DA and its synthesis is associated in part with SAL‐induced PRL secretion in goats.     

Molecular evolution of multiple arylalkylamine N-acetyltransferase (AANAT) in fish

Arylalkylamine N-acetyltransferase (AANAT) catalyzes the transfer of an acetyl group from acetyl coenzyme A (AcCoA) to arylalkylamines, including indolethylamines and phenylethylamines. Multiple aanats are present in teleost fish as a result of whole genome and gene duplications. Fish aanat1a and aanat2 paralogs display different patterns of tissue expression and encode proteins with different substrate preference: AANAT1a is expressed in the retina, and acetylates both indolethylamines and phenylethylamines; while AANAT2 is expressed in the pineal gland, and preferentially acetylates indolethylamines. The two enzymes are therefore thought to serve different roles. Here, the molecular changes that led to their specialization were studied by investigating the structure-function relationships of AANATs in the gilthead seabream (sb, Sperus aurata). Acetylation activity of reciprocal mutated enzymes pointed to specific residues that contribute to substrate specificity of the enzymes. Inhibition tests followed by complementary analyses of the predicted three-dimensional models of the enzymes, suggested that both phenylethylamines and indolethylamines bind to the catalytic pocket of both enzymes. These results suggest that substrate selectivity of AANAT1a and AANAT2 is determined by the positioning of the substrate within the catalytic pocket, and its accessibility to catalysis. This illustrates the evolutionary process by which enzymes encoded by duplicated genes acquire different activities and play different biological roles.     

基于四(5,6 二氢1,4 二噻英) 四氮杂卟啉修饰玻碳电极对多巴胺的选择性检测

将四(5,6-二氢-1,4-二噻英)四氮杂卟啉(FePz(dtn)4)通过电沉积的方式固载在玻碳电极上,该电极在抗坏血酸(AA)和尿酸(UA)等干扰物存在下,可选择性地检测多巴胺(DA).对比裸电极,在循环伏安测量中修饰过后的电极在氧化电位处对DA表现出良好的电催化活性.并且出现一对可逆的氧化还原峰,阳极和阴极的电位值分别为0.182V和0.142V.在电解质溶液中氧化峰电流随着DA的浓度线性增加.两个线性范围分别是1～10和10～200μg/mL,相关系数分别为0.996 7和0.998 8.检出限为0.3μg/mL.     

鱼藤酮对小鼠脑神经递质多巴胺及其代谢产物的影响

研究了注射鱼藤酮对C57BL/6N小鼠神经递质多巴胺的影响。给小鼠皮下注射鱼藤酮(10 mg/kg)两次,间隔2 h,在第2次注射8 h后分离脑组织样品,并应用高效液相色谱仪配电化学检测器,测定了小鼠脑内多巴胺(DA)及其主要代谢物3,4-二羟苯酰乙酸(DOPAC)和高香草酸(HVA)的水平。结果表明,第2次注射8 h后,鱼藤酮处理组的脑内DA、DOPAC和HVA水平分别比对照组高40.5%、544.4%和168.2%,差异显著(P<0.01)。实验显示,鱼藤酮对多巴胺能神经系统具有毒性作用。     

Effects of different doses of L-dopa on rotational behavior and amounts of cells expressing D2 receptors in hemiparkinsonian rats

AIM：To observe the effects of different doses of L-dopa on the rotational behavior and amounts of cells expressing D₂ receptors in striatum in hemiparkinsonian rats.METHODS：A hemiparkinsonian model was established in rats by pretreatment with 6-hydroxydopamine.The D₂ receptor expression were detected by immunohistochemical staining.The numbers of rotations induced by apomorphine was counted within 30 min before and after L-dopa (10 mg·kg^-1·d^-1,50 mg·kg^-1·d-^-1 or 100 mg·kg^-1·d^-1,ip) was introduced to Parkinson’s disease (PD) model rats for 15 days.RESULTS：In successful PD model rats,the increased percentage of D₂ receptor in lesioned side compared with intact side was associated linearly with the numbers of rotations within 30 min (r=0.927,P<0.01).After high dose of L-dopa intervention to PD model,the numbers of rotations decreased significantly (P<0.05),the amounts of cells expressing D₂ receptor at the lesioned side striatum decreased significantly (P<0.01).CONCLUSION：After high dose of L-dopa intervention,rotation behavior of PD rats improves,and D₂ receptor is down-regulated significantly.     

Novel polymorphism of the canine dopamine receptor D4 gene intron II region

Various dog breeds are remarkably different from each other not only in their sizes and shapes but also in behavioral traits, suggesting that some of these characteristics are under genetic control. However, little is known about genes related to behavioral traits in canine species. In humans, it has been reported that the dopamine receptor D4 gene (DRD4) includes polymorphism at several regions that relate to personality or psychiatric disorders. In an earlier study by the authors of the present study, the polymorphisms in canine DRD4 exon III and exon I regions were reported. In the present study, a novel polymorphism in canine DRD4 intron II was found based on a 17 base pair insertion/deletion, and the two alleles detected were named P (shorter allele) and Q (longer allele). The allelic distribution in 28 breeds of dog, including a total of 1114 unrelated individuals, were then investigated. Both P and Q alleles were detected in most of the breeds investigated; however, the frequencies of P and Q differed greatly between breeds. With respect to classification based on breed origin, P and Q alleles were frequent in Occidental and Oriental breeds, respectively. Furthermore, two subspecies of wolves, the ancestors of dogs, were analyzed for the comparison of allele frequencies with dogs, and the P allele was predominant in both European and Chinese wolves.     

Descending thoracic aortic blood flow parameters during emergent surgery in anesthetized critically ill dogs

Objective: To explore the potential value of transesophageally‐determined descending thoracic aortic blood flow parameters in critically ill dogs undergoing surgery. Design: Observational case series. Setting: Private small animal referral hospital. Animals: Ten anesthetized critically ill dogs that underwent emergent surgery. Interventions: Placement of the ultrasonic transesophageal probe. Measurements and main results: Transesophageally‐determined descending thoracic aortic blood flow, stroke volume, blood velocity, blood acceleration, left ventricular ejection time interval, and heart rate parameters were recorded every minute. Systolic and mean arterial blood pressures were non‐invasively determined and recorded at 1–5 minute intervals. The anesthetist and surgeon were blinded to the descending thoracic aortic blood flow parameters. All dogs received fluid challenges as part of their management, and 2 dogs received dopamine. The variability of the descending thoracic aortic blood flow parameters within each dog was greater than has been reported in non‐critically ill anesthetized dogs. Consistent trends in descending thoracic aortic blood flow parameters after fluid challenges were not found. An escalating dopamine infusion was, however, accompanied by increasing aortic blood flow, stroke volume, acceleration, and peak velocity. Conclusions: Descending thoracic aortic blood flow parameters may eventually be useful for evaluating the responses to and suggesting the need for cardiovascular interventions during emergent surgeries in anesthetized critically ill canine patients. For this to occur, more experience with this technology will be required.     

L-NAME在大鼠失血性低血压期间对多巴胺与去甲肾上腺素升压效应的影响

目的：观察大鼠失血性低血压期间，一氧化氮（NO）和一氧化氮合酶减少对多巴胺（DA）与去甲肾上腺素（NE）升压效应的影响。方法；戊巴比妥钠麻醉的SD大鼠24只，随机分为DA实验组与对照组各5只，NE实验组与对照组各7只。实验组失血前静脉注射NG－nitro－L－argininemethylester（L－NAME，1mg／kg体重），回输血液后静脉注射L－arginine（L－Arg，100mg／kg体重），对照组不作任何处理。股动脉抽血使平均动脉压（MAP）降至5．0kPa左右，维持120min，于低血压期间，每隔30min，及回输血液后10min，静脉注射L－Arg后10min等时间点，静脉注射DA（20μg／kg体重）或NE（10μg／kg体重）。结果：经L－NAME处理的大鼠，存活时间延长，回输血液后，BP基本恢复至失血前水平，无论在低血压期间或血液回输后，对DA、NE的升压反应均增强，实验组MAP回升值明显高于对照组（P＜0．05），L－Arg可抑制此作用。心率（HR）反应在L－NAME处理鼠与对照鼠之间无差异。结论。在重度失血性低血压期间，L－NAME可以增强血管对DA、NE等缩血管药物的敏感性，在动物的存活和血管张力的调节方面起有益作用。     

Differential effects of photoperiod and temperature on hypothalamic monoaminergic activity in the teleost Channa punctatus (Bloch)

In Channa punctatus maintained under ambient photothermal conditions (10.5L:13.5D; 13 ± 2°C) in the postspawning season, hypothalamic dopamine (DA) and norepinephrine (NE) content varied diurnally, but serotonin (5-HT) and monoamine oxidase (MAO) did not. Exposure of the fish to high temperature (25 ± 2°C), with or without altering the photopheriod, increased the NE and DA content, and NE turnover but decreased DA turnover. Increasing the photoperiod (16L:8D) alone had no significant effect on catecholaminergic (CA) content or activity. When the fish were exposed to long photoperiod, with or without altering the temperature, a day-night variation in 5-HT content and activity was induced in the postspawning season. An increase in temperature alone had no significant effect on 5-HT content or activity. Hypothalamic MAO activity was elevated in fish exposed to high temperature alone, or in combination with long photoperiod, but was not affected significantly by long photoperiod treatment. These results indicate that CA activity is influenced largely by ambient high temperature, whereas serotonergic activity is controlled primarily by photoperiod, with high temperature having an additive effect. MAO activity seems to be influenced by both temperature and photoperiod in this species.