Effect of Monoamine Oxidase Gene Knockout on Dopamine Metabolism in Mouse Brain Structures

Experiments were performed on knockout Tg8 mice lacking monoamine oxidase A gene that plays a major role in dopamine catabolism. The study by the method of high-performance liquid chromatography revealed considerable regional differences in the contents of dopamine and its metabolite dihydroxyphenylacetic acid in brain structures of these animals. Tg8 mice differed from the parent C3H/HeJ strain by low level of dihydroxyphenylacetic acid in the striatum, midbrain, hypothalamus, and hippocampus and high concentration of dopamine in the striatum. No differences were revealed in the contents of dopamine and dihydroxyphenylacetic acid in the frontal cortex and amygdala. The 2.4-4.8-fold decrease in the content of dihydroxyphenylacetic acid in various brain structures was not accompanied by changes in dopamine concentration. These data reflect the effective compensation for deficiency of dopamine metabolism. Our results suggest that monoamine oxidases A and B and catechol-O-methyltransferase play different roles in dopamine metabolism in various brain structures.     

单胺氧化酶对老年心力衰竭患者临床应用价值

目的 研究老年心力衰竭患者的单胺氧化酶变化情况及单胺氧化酶对老年心力衰竭诊断及病情评估的临床应用价值。方法 选择2012年1月~2018年1月在我院心内科＞60岁老年慢性心力衰竭住院患者412 例,按纽约心脏病协会（NYHA）心功能分级分为四组,心力衰竭I级31例、Ⅱ级78例、Ⅲ级182例、Ⅳ级121例,选取同期健康体检老人62例为对照组,所有患者进行血清单胺氧化酶及NT-proBNP、超敏C反应蛋白浓度检测对比;同时比较收缩性心力衰竭者与舒张性心力衰竭者单胺氧化酶及浓度变化,研究单胺氧化酶与超声心动图指标左心室射血分数、左心室舒张末期内径的相关性。结果 单胺氧化酶对照组与心力衰竭I级组比较,差异无统计学意义（P＞0.05）,心力衰竭Ⅱ~Ⅳ级组单胺氧化酶、NT-proBNP、Hs-CRP均高于心力衰竭Ⅰ级组与对照组,差异有统计学意义（P＜0.05）。收缩性心力衰竭平均MAO、Hs-CRP、NT-proBNP、LVEDD 较高,舒张性心力衰竭平均LVEF较高;老年心力衰竭患者单胺氧化酶与LVEF 呈负相关（r=-0.647,P＜0.05）;与LVEDD 呈正相关（r =0.726,P＜0.05）。结论 单胺氧化酶能较好的反映心力衰竭患者心脏结构及功能的变化,在心力衰竭的早期诊断、病情及预后的评估有重要的临床应用价值。     

Characteristics of the Behavioral Phenotype of BALB/C Mice

Neuroscience and Behavioral Physiology - The existence of specific behavioral characteristics which can be regarded as autistic spectrum disorder (ASD) in BALB/c mice was detected and confirmed,...     

Altered Expression of Tyrosine Hydroxylase in the Locus Coeruleus Noradrenergic System in Citalopram Neonatally Exposed Rats and Monoamine Oxidase A Knock Out Mice

In rodents, noradrenergic (NE) locus coeruleus (LC) neurons are well known to express tyrosine hydroxylase (TH) immunoreactivity. However, due to its very low enzyme activity, NE cortical fibers do not typically express TH immunoreactivity, thus dopamine‐β‐hydroxylase (DBH) immunoreactivity is commonly utilized as a marker for NE cortical fibers. In this study, we performed double and/or triple immunofluorescent staining using antibodies against TH, DBH, and/or norepinephrine transporter (NET) to investigate the altered NE TH expression of cortical fibers in citalopram (CTM)‐exposed rats and monoamine oxidase (MAO) A knock out (KO) mice. We have noted the following novel findings: (1) neonatal exposure to the selective serotonin reuptake inhibitor (SSRI) CTM enhanced NE TH immunoreactive fibers throughout the entire neocortex, and a few of them appeared to be hypertrophic; (2) slightly enhanced NE cortical TH immunoreactive fibers were also noted in MAO A KO mice, and many of them revealed varicosities compared with the rather smooth NE cortical TH immunoreactive fibers in wild‐type (WT) mice; (3) LC dendrites of MAO A KO mice exhibited beaded morphology compared with the smooth LC dendrites in WT mice. Our findings suggest that both genetic and environmental factors during early development may play a critical role in the regulation and proper function of NE TH expression in the neocortex. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.     

Effect of Afobazole on Mitochondrial Monoamine Oxidase A Activity <Emphasis Type="Italic">In Vitro</Emphasis>

Selective anxiolytic afobazole (1 mM) inhibits monoamine oxidase A activity in mitochondria from rat brain and liver (IC₅₀ 0.36 and 0.43, respectively). Effect of the compound does not depend on the time of preincubation with mitochondria. Triple washout of mitochondria is followed by complete recovery of initial enzyme activity.     

载脂蛋白E基因敲除小鼠在动脉粥样硬化研究中的应用

载脂蛋白E基因敲除小鼠是目前在动脉粥样硬化 (AS)研究领域中应用最多的基因工程动物。参考国内外应用载脂蛋白E基因敲除小鼠研究AS的有关文献 ,就其AS病灶形成的规律及形态学改变 ,有氧运动和饮食对该小鼠AS病灶的影响 ,关于调脂药物和其它药物研究情况 ,骨髓移植和基因治疗对该种小鼠AS病灶的影响等方面作一综述 ,以期将这种基因工程小鼠动物模型更广泛地应用于中西医药研究     

Aggression,Digit Ratio and Variation in Androgen Receptor and Monoamine Oxidase A Genes in Men

Variation in prenatal exposure to androgens is thought to be responsible for some of the individual differences in aggressive behavior among adults. A putative indicator of prenatal testosterone exposure, 2D:4D (the index to ring finger length) ratios have shown a weak correlation with aggression. Variation in sensitivity of the androgen receptor, resulting from polymorphism in the AR gene, is also thought to influence the relative expression of sexually dimorphic traits within each sex, including aggressive behavior and 2D:4D. Here we examine variation in aggression, 2D:4D, and polymorphism in the AR and MAO-A genes in a sample of 188 men. We find no evidence of AR gene influence on right hand 2D:4D, and a weak trend towards more feminine-typical left hand 2D:4D in men with more sensitive androgen receptors. Men with more sensitive androgen receptors tended to score lower on many of the subscales of the Aggression Questionnaire and Indirect Aggression Questionnaire. We found no influence of MAO-A allele on either digit ratio or aggressive behavior. We conclude that more masculine-typical 2D:4D does not reflect greater sensitivity to testosterone through variation in this locus on the AR gene, and that AR alleles conferring greater sensitivity to testosterone are associated with lower, not higher propensity to aggression.     

Computational Stress Analysis of Atherosclerotic Plaques in ApoE Knockout Mice

The aortic sinus lesions of apolipoprotein E knockout (ApoE KO) mice seldom show any signs of fibrous cap disruption, whereas cap ruptures have been recently reported in the proximal part of their brachiocephalic arteries (BCA). We use histology based finite element analysis to evaluate peak circumferential stresses in aortic and BCA lesions from six 42–56 week-old fat-fed ApoE KO mice. This analysis is able to both explain the greater stability of aortic lesions in mice and provide new insight into the BCA lesion as a model for the stability of human lesions with and without microcalcifications in their fibrous caps. The predicted average peak stress in fibrous caps of aortic lesions of 205.8 kPa is significantly lower than the average value of maximum stresses of 568.8 kPa in BCA caps. The aortic plaque stresses only slightly depend on the cap thickness, while BCA lesions demonstrate an exponential growth of peak cap stresses with decreasing cap thickness similar to human vulnerable plaques. Murine BCA ruptured lesions with mean cap thickness of 2 μm show stresses ≈1400 kPa, three times higher than human ruptured plaques with a mean cap thickness of 23 μm without microcalcifications in the cap, but nearly identical to the peak stress around an elongated microcalcification with aspect ratio 2 in a human thin cap ≈50 μm thick. We predict biomechanical stress patterns in mouse BCA close to human vulnerable plaques without microcalcification in the cap, while aortic lesions show stress tendency similar to stable lesions in human.     

Early Resistance of Interleukin-10 Knockout Mice to Acute Systemic Candidiasis

In contrast to immunocompetent controls, interleukin-10 (IL-10) knockout (KO) mice eliminated an experimental intravenous inoculation with Candida albicans from their kidneys. Improved clearance of C. albicans from the kidneys of IL-10 KO mice was evident at 24 h after intravenous challenge with the fungus. Conversely, mice with a deletion of the IL-4 cytokine gene were more susceptible to systemic candidiasis than were immunocompetent controls. The hyperresistance of IL-10 KO mice to acute systemic candidiasis did not seem to correlate with nitric oxide-mediated immunity, but rather, it appeared to be associated with more efficient effector function of innate cells, possibly neutrophils. In support of the latter hypothesis, we observed that neutrophils from IL-10 KO mice were more efficient at killing C. albicans blastoconidia and hyphae than were neutrophils from immunocompetent control mice. Neither IL-10 KO nor IL-4 KO mice that were monoassociated with C. albicans for 4 weeks showed any histologic evidence of systemic candidiasis of endogenous origin. In contrast to systemic candidiasis, we observed no significant (P < 0.05) differences in susceptibility among IL-10 KO, IL-4 KO, and wild-type (immunocompetent) mice to orogastric candidiasis. Our results suggest that IL-10 exerts a negative effect on the early, innate response to acute systemic candidiasis; however, in comparison to immunocompetent control (wild-type) mice, neither IL-10 nor IL-4 deficiency enhanced susceptibility to orogastric candidiasis.     

Megalin Knockout Mice as an Animal Model of Low Molecular Weight Proteinuria

Megalin is an endocytic receptor expressed on the luminal surface of the renal proximal tubules. The receptor is believed to play an important role in the tubular uptake of macromolecules filtered through the glomerulus. To elucidate the role of megalin in vivo and to identify its endogenous ligands, we analyzed the proximal tubular function in mice genetically deficient for the receptor. We demonstrate that megalin-deficient mice exhibit a tubular resorption deficiency and excrete low molecular weight plasma proteins in the urine (low molecular weight proteinuria). Proteins excreted include small plasma proteins that carry lipophilic compounds including vitamin D-binding protein, retinol-binding protein, alpha(1)-microglobulin and odorant-binding protein. Megalin binds these proteins and mediates their cellular uptake. Urinary loss of carrier proteins in megalin-deficient mice results in concomitant loss of lipophilic vitamins bound to the carriers. Similar to megalin knockout mice, patients with low molecular weight proteinuria as in Fanconi syndrome are also shown to excrete vitamin/carrier complexes. Thus, these results identify a crucial role of the proximal tubule in retrieval of filtered vitamin/carrier complexes and the central role played by megalin in this process.     

Effect of Dexamethasone on Immune Response of Mice with Different Behavioral Types

Experiments on a model of paired sensory contact showed that dexamethasone effectively suppressing the response to ACTH not only prevented immunosuppression in male C57Bl/6J mice with submissive behavior formed during different periods of confrontation testing (days 10 and 20), but also stimulated the immune response in comparison with the control. Immune response in aggressive animals after 20-day confrontations was higher than in controls and submissive mice and did not change after dexamethasone injection. The authors conclude that the immunosuppressive effect in submissive animals is realized through ACTH, which little contributes into immunomodulation in aggressive mice.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 5, pp. 550–552, May, 2005     

Behavioral Analysis of Narcoleptic Episodes in Orexin-Deficient Mice

Orexin-deficient mice express narcoleptic episodes which mirror some of the main symptoms of human narcolepsy. Therefore, they are often used in narcolepsy research. However, little is known about some behavioral characteristics of narcoleptic episodes, e.g. about episode types, duration, and variability. In the present study, 351 narcoleptic episodes of orexin-deficient mice were behaviorally characterized. Based on this data, we describe different onset and progression episodes types. These episode types affected episode duration, i.e. abrupt onsets and ‘shaking’-like movements increased episode duration. Our data suggests that promoting motor activity enhances the frequency of narcoleptic episode. Inter-individual variability of episode frequency and duration was large; however, the intra-individual frequency was relatively stable. Based on these findings we suggest the following to increase the statistical power of experiments in orexin-deficient mice: Using a pre-screen and selecting the mice with decent episode frequency, using an enriched environment as well as using repeated-measure designs.     

Tanshinone IIA Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice Infected with <Emphasis Type="Italic">Porphyromonas gingivalis</Emphasis>

Tanshinone IIA (TSA), a pharmacologically active component isolated from Danshen, may prevent cardiovascular diseases due to its anti-inflammatory, anti-oxidative, and anti-adipogenic effects. Porphyromonas gingivalis, a major periodontal pathogen, may contribute to the progression of atherosclerosis. Here, we studied the effects of TSA on atherosclerosis in ApoE^?/? mice with P. gingivalis infection. Eight-week-old ApoE^?/? mice were randomized to (a) phosphate-buffered saline (PBS), (b) P. gingivalis, and (c) P. gingivalis + TSA (60 mg kg^?1 day^?1). The mice were injected with (a) PBS, or (b) and (c) P. gingivalis 3 times per week for a total of 10 times. After 8 weeks, atherosclerotic risk factors in serum and in heart, aorta, and liver tissues were analyzed in all mice using Oil Red O, atherosclerosis cytokine antibody arrays, enzyme-linked immunosorbent assay (ELISA), real-time PCR, and microRNA array. CD40, G-CSF, IFN-γ, interleukin (IL)-1β, IL-6, MCP-1, MIP-3α, tumor necrosis factor-α (TNF-α), and VEGF were attenuated by TSA in atherosclerosis cytokine antibody arrays. TSA-treated mice showed a significant reduction of C-reactive protein (CRP), ox-LDL, IL-1β, IL-6, IL-12, and TNF-α in ELISA data. Real-time PCR analyses showed that TSA decreased the expression of CCL-2, CD40, IL-1β, IL-6, TNF-α, and MMP-2 in heart and aorta tissues. Moreover, hepatic CRP was downregulated by TSA, although FASN and HMG-CoA were not. The relative expressions of miR-146b and miR-155 were elevated by P. gingivalis infection and were downregulated by TSA treatment. These results suggest that TSA was a potential therapeutic agent that may have the ability to prevent P. gingivalis-induced atherosclerosis associated with anti-inflammatory and anti-oxidative effects.