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Influence of Age and Strain on Striatal Dopamine Loss in a Genetic Mouse
Model of Lesch-Nyhan Disease 总被引:3,自引:1,他引:2
H. A. Jinnah M. D. Jones B. E. Wojcik† J. D. Rothstein E. J. Hess T. Friedmann† & G. R. Breese‡ 《Journal of neurochemistry》1999,72(1):225-229
Abstract : Lesch-Nyhan disease is a neurogenetic disorder caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit a characteristic pattern of neurological and behavioral features attributable in part to dysfunction of basal ganglia dopamine systems. In the current studies, striatal dopamine loss was investigated in five different HPRT-deficient strains of mice carrying one of two different HPRT gene mutations. Caudoputamen dopamine concentrations were significantly reduced in all five of the strains, with deficits ranging from 50.7 to 61.1%. Mesolimbic dopamine was significantly reduced in only three of the five strains, with a range of 31.6-38.6%. The reduction of caudoputamen dopamine was age dependent, emerging between 4 and 12 weeks of age. Tyrosine hydroxylase and aromatic amino acid decarboxylase, two enzymes responsible for the synthesis of dopamine, were reduced by 22.4-37.3 and 22.2-43.1%, respectively. These results demonstrate that HPRT deficiency is strongly associated with a loss of basal ganglia dopamine. The magnitude of dopamine loss measurable is dependent on the genetic background of the mouse strain used, the basal ganglia sub-region examined, and the age of the animals at assessment. 相似文献
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Khue Vu Nguyen Robert K. Naviaux William L. Nyhan 《Nucleosides, nucleotides & nucleic acids》2017,36(11):704-711
Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. The authors report a novel point mutation that led to HGprt-related neurological dysfunction (HND) in a family in which there was a missense mutation in exon 6 of the coding region of the HPRT1 gene: g.34938G>T, c.403G>T, p.D135Y. Molecular diagnosis is consistent with the genetic heterogeneity of the HPRT1 gene responsible for HGprt deficiency. It allows fast, accurate carrier detection and genetic counseling. 相似文献
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Wei-Xia Jian Wen-Hui Peng Hai-Ling Li Qi-Wen Feng Wei-Xing Wang Qing Su 《Nucleosides, nucleotides & nucleic acids》2013,32(4):189-195
Lesch-Nyhan disease (LND) is caused by deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT). The aim of the present study is to characterize the molecular deficiency of a clinical diagnosed Chinese patient with attenuated variant of LND. The coding region and the intron-exon boundaries of HPRT1 gene were sequenced by standard methods, and HPRT activity was assayed by HPLC method. Structure analysis was performed to estimate the consequence of the mutant of HPRT1 gene. A new mutation c.245T>G (p.Ile82Ser) was identified in this patient, and heterozygous mutation was found in the patient's mother. The activity of HPRT in the patient was completely undetectable. Structure study indicates that the mutation of p.Ile82Ser may lead to loss of hydrophobic side chain and disrupt its normal conformation of HPRT protein. It is helpful for diagnosis of LND that sequencing analysis of HPRT1 gene is performed in male infant and juvenile with hyperuricaemia and neurologic dysfunction in Chinese. 相似文献
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Michael R. Lowe Karen Miller-Kovach Nema Frye Suzanne Phelan 《Obesity (Silver Spring, Md.)》1999,7(1):51-59
LOWE, MICHAEL R, KAREN MILLER-KOVACH, NEMA FRYE, AND SUZANNE PHELAN. An initial evaluation of a commercial weight loss program: short-term effects on weight, eating behavior, and mood. Obes Res. 1999;7:51–59. Objective : This paper describes an initial, 4-week evaluation of a commercial weight loss program. Research Methods and Procedures : Respondents (n = 985) to newspaper advertisements in two metropolitan areas were assigned to 4 weeks of either the Weight Watchers program or to a Self-Help condition. Weight loss, psychological vitality, and eating behavior were evaluated before and after the 4-week intervention. Results : Weight Watchers participants showed greater improvements than Self-Help participants on all measures; weight losses averaged 1.87 and 0.77 kg, respectively. The superior outcomes shown by Weight Watchers participants on measures of vitality and eating behavior were still evident when extent of weight loss was controlled. Weight losses across different sites, incomes, and levels of obesity were similar. Discussion : Although the present study's intervention and outcome assessments were short-term, the promising results obtained suggest that longer term studies should be undertaken. 相似文献
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S-腺苷蛋氨酸(S-adenosyl-L-methionine,SAMe)是一种天然分子存在于人体所有细胞中,在肝脏、肾上腺以及松果体中具有较高浓度,在大脑中亦均匀分布。S-腺苷蛋氨酸通过抗氧化自由基及促进肝细胞再生等机制对肝细胞具有多重保护作用长久以来被广泛应用于肝病所致的肝内胆汁淤积、抗肝纤维化等治疗。近年来,研究亦发现S-腺苷蛋氨酸可增加患者脑中神经元膜的流动性及促进兴奋性神经递质的产生等对改善肝病患者情绪、治疗肝病患者抑郁症等方面具有重要的双重作用。通过静脉或口服用药,均可提高患者脑脊液中SAMe浓度,对于轻、中度抑郁患者的辅助治疗,更具安全性、有效性,这为人类的"生理-心理"疾病的治疗带来更广阔的应用前景。现将其对肝病患者抗抑郁的作用机制及临床应用综述如下。 相似文献
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Khue Vu Nguyen 《Nucleosides, nucleotides & nucleic acids》2015,34(10):674-690
Recently, epigenetic regulation of alternative APP pre-mRNA splicing in the Lesch-Nyhan syndrome (LNS) has been studied (see Ref. 7) and showed for the first time, the presence of several APP-mRNA isoforms encoding divers APP protein isoforms ranging from 120 to 770 amino acids (with or without mutations and/or deletions). Here, by continuing on this work, I identified, for the first time new APP-mRNA isoforms with a deletion followed by an insertion (INDELS) in LNS and LNVs patients:c.19_2295delinsG166TT…GAGTCC…CTTAGTC…TCT489,p.Leu7Valfs*2;c.19_2295 delinsG169TT…GAGACC…CTTGGTC…TCT492,p.Leu7Valfs*2;and c.16_2313delinsG84CC…CAT616,p.Leu7Hisfs*45. A role of genomic rearrangements of APP gene via the Fork Stalling and Template Switching (FoSTeS) mechanism leading to INDELS was suggested. Epistasis between mutated HPRT1 and APP genes could be one of the factors of epigenetic modifications responsible for genomic rearrangements of APP gene. My findings accounted for epigenetic mechanism in the regulation of alternative APP pre-mRNA splicing as well as for epigenetic control of genomic rearrangements of APP gene may provide therefore new directions not only for investigating the role of APP in neuropathology associated with HGprt-deficiency in LNS and LNVs patients but also for the research in neurodevelopmental and neurodegenerative disorders by which APP gene involved in the pathogenesis of the diseases such as autism, fragile X syndrome (FXS), and Alzheimer's disease (AD) with its diversity and complexity, especially for sporadic form of AD (SAD). An accurate quantification of various APP-mRNA isoforms in brain tissues for detection of initial pathological changes or pathology development is needed and antisense drugs are the potential treatments. 相似文献
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M. A. Novak J. H. Kinsey M. J. Jorgensen T. J. Hazen 《American journal of primatology》1998,46(3):213-227
Self-injurious behavior (SIB) occurs in about 10% of individually housed monkeys. Monkeys with SIB bite their own bodies frequently, occasionally inflicting wounds as a result. At present, there is no standard treatment for this phenomenon. We examined the effectiveness of puzzle feeders in alleviating SIB in monkeys with a veterinary record of self-inflicted wounding. Two groups of monkeys (SIB and controls) were exposed to puzzle feeders for a 6 week period. Three levels of maze difficulty were examined. All monkeys used the feeders, but manipulation was confined to a brief period immediately after the feeders were loaded each day (1000 h) and was infrequent during the later sampling periods (1100 and 1400 h). The most difficult maze yielded a slight increase in usage at 1100 h. During the puzzle feeder phase, whole body stereotypies, including pacing and rocking, were reduced substantially in all monkeys at 1000 h when feeder manipulation was at its highest. However, self-biting in the SIB group was unchanged. Some monkeys actually bit themselves while manipulating the feeder. Long-term effects on abnormal behavior were assessed by comparing behavior during the feeder phase to baseline periods and to a phase in which the monkeys were provisioned with treats placed directly into their food box. Whole body stereotypies, including pacing, were reduced during both treatment phases; however, the reduction was associated only with the 1000 h observation. Puzzle feeders were more effective than treats alone in alleviating whole body stereotypies. Self-biting was unchanged through all phases. Puzzle feeders are beneficial from the perspective of eliciting manipulation. They also yield transient reductions in whole body stereotypy, an effect that does not extend beyond the direct manipulation of the feeder. Puzzle feeders are ineffective in alleviating self-injurious behavior. Am. J. Primatol. 46:213–227, 1998. © 1998 Wiley-Liss, Inc. 相似文献
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This work is conducted to investigate the hierarchical structure,mechanical behavior and fracture resistance of grass carp scales with different water contents (hydrated and dehydrated) and load conditions (uniaxial,biaxial and punch tests).The whole cross-section of scales is investigated,and it is found that the bony layer displays discontinuity and partly embeds in collagen layer.Four different locations are considered under both tensile and punch tests.The results of the uniaxial tensile test show a correlation between the failure mode and the distribution of surface morphology on scales.The biaxial test results show that there are minor differences in the tensile strength and the Young'modulus compared with those of the uniaxial tests,but the ultimate strain is about 20%-50%.Puncture tests are also conducted with different size of needles and different hardness silicon rubbers as substrate.The results show that the puncture force and deformation are dependent on the size of needle and the hardness of substrate.The failure pattern of scales is related to the water content.Radial cracks occur in the bony layer of hydrated scale,and the collagen fibers twist around the puncture site.However,the shear failure occurs in the bony layer of dehydrated scale. 相似文献
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The present study examined effects of the combined administration of naloxone (NX) and indomethacin (IM) on nigrostriatal catecholamines and locomotor activity after intranigral lipopolysaccharide (LPS) injection in Sprague-Dawley rats. NX plus IM was given 3 days after LPS injection; it significantly (P < .05) reversed LPS inflammation on nigrostriatal dopamine (DA) and nigral serotonin (5-HT) and nigral homovanillic acid (HVA)/DA ratio and nigrostriatal 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio. It also tended to ameliorate the locomotor hyperactivity. However, NX plus IM given 30 min before LPS could not satisfactorily protect against LPS's damage both biochemically and behaviorally. These results reveal that NX plus IM may protect against LPS on DA, 5-HT, and motor function after LPS injection but not before. Thus it suggests that the combined treatment of NX and IM gives a potent therapy, but not prevention, of LPS-induced inflammation and also protect nigrostriatal dopaminergic and serotoninergic systems against LPS in rats. 相似文献
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目的:研究s-腺苷蛋氨酸治疗胆汁淤积性肝病伴抑郁/焦虑患者的临床效果。方法:选择2011年3月-2013年3月我院收治的51例不同病因的胆汁淤积性肝病(药物性肝损害13例、慢性乙型肝硬化14例、酒精性肝硬化11例、自身免疫性肝病6例、肝癌5例、胆管癌2例)并抑郁/焦虑的患者,予s-腺苷蛋氨酸1.0g治疗2周,应用SDS/SAS量表分别评估和比较治疗前后各组患者抑郁/焦虑程度的评分情况。结果:S-腺苷蛋氨酸治疗后,所有组别胆汁淤积性肝病肝病改善的临床总有效率94.12%,其中药物性肝损害、慢性乙型肝硬化、酒精性肝硬化、自身免疫性肝硬化总有效率均为100.00%,肝癌的有效率为60.00%,胆管癌的有效率为50.00%,药物性肝损害患者临床疗效与其他各组有差异(P〈0.05);药物性肝病患者SDS和SAS评分均较治疗前显著降低(P〈0.05)。而慢性乙型肝硬化、酒精性肝硬化、自身免疫性肝病、肝癌、胆管癌患者SDS和SAS评分与治疗前相比均无统计学差异(P〉0.05)。结论:S-腺苷蛋氨酸可改善药物性胆汁淤积性肝病并轻、中度抑郁/焦虑患者的肝功能,并有效减轻其抑郁/焦虑情绪。 相似文献
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目的:研究S-腺苷蛋氨酸治疗胆汁淤积性肝病伴抑郁/焦虑患者的临床效果。方法:选择2011年3月~2013年3月我院收治的51例不同病因的胆汁淤积性肝病(药物性肝损害13例、慢性乙型肝硬化14例、酒精性肝硬化11例、自身免疫性肝病6例、肝癌5例、胆管癌2例)并抑郁/焦虑的患者,予S-腺苷蛋氨酸1.0 g治疗2周,应用SDS/SAS量表分别评估和比较治疗前后各组患者抑郁/焦虑程度的评分情况。结果:S-腺苷蛋氨酸治疗后,所有组别胆汁淤积性肝病肝病改善的临床总有效率94.12%,其中药物性肝损害、慢性乙型肝硬化、酒精性肝硬化、自身免疫性肝硬化总有效率均为100.00%,肝癌的有效率为60.00%,胆管癌的有效率为50.00%,药物性肝损害患者临床疗效与其他各组有差异(P0.05);药物性肝病患者SDS和SAS评分均较治疗前显著降低(P0.05)。而慢性乙型肝硬化、酒精性肝硬化、自身免疫性肝病、肝癌、胆管癌患者SDS和SAS评分与治疗前相比均无统计学差异(P0.05)。结论:S-腺苷蛋氨酸可改善药物性胆汁淤积性肝病并轻、中度抑郁/焦虑患者的肝功能,并有效减轻其抑郁/焦虑情绪。 相似文献
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目的:探讨不同疼痛患者的焦虑、抑郁和患病行为的关系,为疼痛患者临床心理诊断及心理干预提供必要的参考依据.方法:采用多中心合作的方式,抽取北京、西安、重庆等10家医疗单位的513例疼痛患者进行门诊问卷调查,采用医院焦虑抑郁量表(HADS)和患病行为问卷(IBQ)分别进行测量,对不同疾病种类疼痛患者焦虑、抑郁症状差异和患病行为的差异进行比较,并对焦虑、抑郁和患病行为各维度进行相关和多元逐步回归分析.结果:(1)不同疾病种类疼痛患者HADS总分差异有显著性(F=3.20,P<0.05),其中焦虑因子得分差异无统计学意义(F=1.28,P>0.05),抑郁因子得分差异有统计学意义(F=4.45,P<0.01),癌症患者得分[(9.67±4.70)分]显著高于其他疾病种类;不同疾病种类疼痛患者IBQ总分差异有显著性(F=5.44,P<0.01),其中负性情绪因子得分(F=3.11,P<0.05)和患病角色因子得分(F=9.28,P<0.01)差异有统计学意义,癌症患者得分最高[分别为(9.50±3.68)分和(8.10±1.82)分],显著高于其他疾病种类,行为反应因子得分差异无统计学意义(F=0.80,P>0.05);(2)负性情绪和行为反应因子均与焦虑和抑郁因子呈显著正相关(rmax=0.517,P<0.01;rmin=0.305,P<0.05),多元逐步回归分析发现:焦虑和抑郁的首要影响因素为行为反应因子(分别为Beta=0.323和Beta=0.368),患病角色在抑郁维度上未进入回归方程.结论:不同疾病种类疼痛患者焦虑、抑郁和患病行为存在差异,患病行为对疼痛患者焦虑及抑郁症状具有正向预测作用. 相似文献
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目的:探讨S-腺苷蛋氨酸对梗阻性黄疸患者术后肝功能及营养状况的影响。方法:选择2010年8月至2012年7月我院肝胆病区收治的90例梗阻性黄疸患者为研究对象,随机分为S-腺苷蛋氨酸治疗组(48例)和对照组(42例),比较和分析静脉滴注S-腺苷蛋氨酸对梗阻性黄疸患者术后第5d、10d肝功能及营养指标的影响。结果:术后5d、10d,两组患者血总胆红素、直接胆红素、谷丙转氨酶、1.谷氨酰转肽酶、碱性磷酸酶水平较术前1d显著降低,且组内比较差异有统计学意义(P〈0.05),治疗组以上指标的下降程度较对照组更明显,差异有统计学意义(P〈0.05)。术后第10d,两组患者的血白蛋白、前白蛋白、转铁蛋白水平较术后第5d显著改善(P〈0.05);术后第5、10d,两组组间血白蛋白、前白蛋白、转铁蛋白水平比较差异有统计学意义(P〈0.05)。结论:梗阻性黄疸患者术后应用腺苷蛋氨酸能促进黄疸消退,加快胆红素的排泄和肝功能的恢复,有利于患者营养状况的改善。 相似文献
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目的:探讨S-腺苷蛋氨酸对梗阻性黄疸患者术后肝功能及营养状况的影响。方法:选择2010 年8 月至2012年7 月我院肝
胆病区收治的90 例梗阻性黄疸患者为研究对象,随机分为S- 腺苷蛋氨酸治疗组(48 例)和对照组(42 例),比较和分析静脉滴注
S-腺苷蛋氨酸对梗阻性黄疸患者术后第5 d、10 d肝功能及营养指标的影响。结果:术后5 d、10 d,两组患者血总胆红素、直接胆
红素、谷丙转氨酶、酌-谷氨酰转肽酶、碱性磷酸酶水平较术前1d 显著降低,且组内比较差异有统计学意义(P<0.05),治疗组以上指
标的下降程度较对照组更明显,差异有统计学意义(P<0.05)。术后第10d,两组患者的血白蛋白、前白蛋白、转铁蛋白水平较术后
第5 d显著改善(P<0.05);术后第5、10 d,两组组间血白蛋白、前白蛋白、转铁蛋白水平比较差异有统计学意义(P<0.05)。结论:梗
阻性黄疸患者术后应用腺苷蛋氨酸能促进黄疸消退,加快胆红素的排泄和肝功能的恢复,有利于患者营养状况的改善。 相似文献
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《Bioscience, biotechnology, and biochemistry》2013,77(8):1866-1868
Psilocybe argentipes is a hallucinogenic mushroom. The present study examined the effects of P. argentipes on marble-burying behavior, which is considered an animal model of obsessive-compulsive disorder. P. argentipes significantly inhibited marble-burying behavior without affecting locomotor activity as compared with the same dose of authentic psilocybin. These findings suggest that P. argentipes would be efficient in clinical obsessive-compulsive disorder therapy. 相似文献
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目的:探讨音乐疗法对阿尔茨海默病(AD)患者睡眠质量、生活质量、认知功能及激越行为的影响。方法:选择2016年8月至2017年10月湖南省脑科医院收治的AD患者50例为研究对象,采用随机数字表法分为观察组和对照组各25例,对照组给予常规药物治疗及认知训练,观察组在对照组的基础上给予音乐疗法辅助治疗,于治疗前、治疗8周,治疗16周采用匹茨堡睡眠质量指数量表(PSQI)、睡眠状况自评量表(SRSS)、生活质量测定量表简表(WHOQOL-BREF)、简易智力状态检查量表(MMSE)、简明精神病评定量表(BPRS)和激越行为量表(CMAI)评价两组治疗效果。结果:两组治疗8周和治疗16周的PSQI评分、SRSS评分、BPRS评分、CMAI评分与治疗前比较均明显降低,且治疗16周与治疗8周比较进一步降低,观察组治疗8周和治疗16周的上述评分均低于对照组(P0.05);WHOQOL-BREF评分、MMSE评分治疗8周和治疗16周与治疗前比较明显提高,且治疗16周与治疗8周比较进一步提高,观察组治疗8周和治疗16周的上述评分均高于对照组(P0.05)。结论:音乐疗法辅助治疗AD可以进一步改善患者的睡眠质量、认知功能和激越行为,提高患者的生活质量。 相似文献
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温泉李红霞张硕凌晨付培德 《现代生物医学进展》2012,12(4):713-715
目的:探讨护理干预对慢性乙肝患者遵医行为的影响。方法:将172例慢性肝炎患者随机分成实验组和对照组,每组各86例。两组均接受常规护理,此外实验组还给予疾病认识、心理疏导、治疗目标、饮食管理、生活行为管理、遵医服药、疾病的自我监测以及控制交叉感染等护理干预。一年后对两组患者进行慢性肝炎相关知识和遵医行为的测评,同时检测两组肝功能指标、并发症的发生率及再次住院次数。结果:实验组遵医行为明显优于对照组且肝功控制优于对照组。结论:护理干预可以提高慢性乙型肝炎患者的遵医行为,对病情的控制有良好的效果。 相似文献
19.
该研究主要探讨了体外高浓度全反式维甲酸(all-trans retinoic acid,ATRA)对SD大鼠骺软骨细胞生物学性状和功能的影响以及体内ATRA对SD大鼠胫骨生长板的影响。以SD大鼠骺软骨细胞为研究对象、ATRA为干预因素,采用CCK-8、细胞流式术、HE染色、Annexin V-FITC细胞凋亡流式检测术、Hoechst染色、细胞划痕、Transwell实验分别评估ATRA处理后细胞的增殖、周期、形态、凋亡及迁移情况,Western blot检测蛋白聚糖、Ⅱ型胶原、X型胶原等相关功能蛋白的变化;以3周雄性SD大鼠为实验对象,分为对照组、60 mg/kg·d ATRA组、80 mg/kg·d ATRA组,进行10天连续ATRA灌胃处理,测量每只SD大鼠灌胃第1天、第10天的头尾长,处理10天后对胫骨生长板进行HE染色。结果表明,ATRA作用SD大鼠骺软骨细胞后,增殖能力减弱且细胞周期被阻滞在S期(P<0.01),细胞形态由三角形、多边形变为长条状,凋亡的发生增多(P<0.01),迁移能力受到抑制(P<0.05)以及Western blot结果显示蛋白聚糖、Ⅱ型胶原、X型胶原等功能相关蛋白较对照组表达均明显降低(P<0.01);对SD大鼠进行ATRA灌胃处理后,与对照组比较,60 mg/kg·d ATRA组和80 mg/kg·d ATRA组的头尾长均变短(P<0.01);胫骨生长板HE染色显示,ATRA灌胃组的生长板变窄甚至闭合。该研究证实了体外高浓度ATRA能够对SD大鼠骺软骨细胞的增殖、迁移起抑制作用,同时能够诱导凋亡,降低相关功能蛋白的表达,在SD大鼠体内证实,过量ATRA可影响生长板软骨内成骨过程,最终使生长板部分或全部提前闭合,进而影响SD大鼠身长的增长。 相似文献
20.
Gasem Mohammad Abu-Taweel 《Saudi Journal of Biological Sciences》2016,23(2):219-228
Cadmium (Cd) exposure can induce acute lethal health-related threats in humans since it has an exceptional ability to accumulate in living organism tissues and cause toxicological effects. Curcumin (Cur) on the other hand has a wide variety of biological activities and several studies have suggested its potential therapeutic or protective effects against several ailments and infections.To study the effect of Cur on the toxicity of Cd, Swiss–Webster strain male and female mice (sixty each) were divided into 6 groups of ten each at random. Group-1 served as the naïve control and received no treatment. Group-2, 3 and 4 were the experimental controls and were administered once a day with a single oral dose of 50% dimethyl sulfoxide (DMSO), Cur (300 mg/kg) or Cd (100 mg/kg) respectively, for 2 weeks. Group-5 and 6 received Cur and Cd in combination once a day orally for 2 weeks except that Cur in a dose of 150 and 300 mg/kg to group 5 and 6 respectively, was administered one hour before Cd administration to both groups.After treatment period, the male animals were subjected to social standard opponent test and females were subjected to the tube restraint tests and thereafter, their blood was collected to measure the blood composition indices and level of reproductive hormones. The animals were sacrificed to collect their brain for the estimation of acetylcholinesterase (AChE).Results indicated that Cd significantly increased nonsocial activities in males and latency to first bite in females, whereas the social activities in males and the number of bites in females were significantly decreased. All measured indices of blood composition and levels of progesterone (female) and testosterone (male) in blood and AChE in their brain tissues were significantly decreased due to Cd treatment.However, administration of Cur along with Cd had an ameliorating effect on all the behavioral and biochemical parameters studied herein and reduced the toxicity of Cd significantly and dose-dependently. Thus, Cur may be beneficial for general health and for protection from Cd intoxication. 相似文献