Acoustic startle response in young and aging C57BL/6J and CBA/J mice

C57BL/6J (C57) mice demonstrate progressive age-related hearing loss during the first year of life, whereas CBA/J (CBA) mice lose little sensitivity through 18 months of age. The acoustic startle response (ASR) was measured in these strains to determine behavioral correlates of aging with and without presbycusis. The stimuli were tone pips (10-ms duration, 1-ms rise-fall) with frequencies of 4, 8, 12, 16, or 24 kHz at intensities of 70, 80, 90, or 100 dB SPL. ASR "thresholds" (the minimum SPL required to elicit ASRs more than 50% of the time) increased with age, and startle amplitudes became smaller in both strains. However, the changes in these startle parameters were much more pronounced in C57 mice, with middle to high frequencies (12-24 kHz) severely affected. The startle latencies at and above ASR "threshold" increased with age in C57 mice, but did not change in CBA mice. The CBA data indicate that aging, per se, has little effect on ASR parameters; the C57 data show that hearing loss is a cogent factor. However, ASR parameters of C57 mice are altered to a greater extent than expected, on the basis of the elevations of absolute sensory thresholds, particularly for middle frequencies (12-16 kHz). Both peripheral and central mechanisms are proposed to account for the discrepancy.     

Sex ratio in CBA X C57BL hybrid mice

The sex ratio and postimplantation mortality were compared for CBA and C57BL mice and (CABxC57BL)F₁ hybrids. Female embryos were found to be more numerous in the progeny of the hybrids. The sex ratio of CBA and C57BL embryos is 1:1. Disturbance of the balanced sex ratio in the progeny of the hybrid mice confirms the conclusion that the genetic characteristics of these mice affect the sex distribution of the embryos. The equal sex ratio in CBA and C57BL mice points to the absence of selective mortality among embryos of either sex during embryogenesis.Department of Embryology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 10, pp. 473–474, October, 1979.     

Asbestos-induced autoimmunity in C57BL/6 mice

Environmental impacts on autoimmunity have significant public health implications. Epidemiological studies have shown associations between exposure to airborne silicates, such as crystalline silica or asbestos, and autoimmunity, but the etiology remains unclear. The purpose of this study was to test the hypothesis that asbestos could lead to a specific pattern of autoantibodies and pathology indicative of systemic autoimmune disease (SAID). Female C57Bl/6 mice were instilled intratracheally with 2 doses x 60 microg/mouse of amphibole asbestos (tremolite), wollastonite (a non-fibrogenic control fiber), or saline alone. Serum samples were collected and urine was checked for protein bi-weekly for 7 months. By 26 weeks, the asbestos-instilled animals had a significantly higher frequency of positive anti-nuclear antibody (ANA) tests compared to wollastonite and saline groups. The majority of positive ANAs showed homogeneous or combined homogeneous/speckled patterns, and tested positive for antibodies to dsDNA and SSA/Ro 52. Serum isotyping showed no significant changes in IgM, IgA, or IgG subclasses. However, there was an overall decrease in the mean IgG serum concentration in asbestos-instilled mice. IgG immune complex deposition was demonstrated in the kidneys of asbestos-instilled mice, with evidence of glomerular and tubule abnormalities suggestive of glomerulonephritis. Flow cytometry demonstrated moderate changes in the percentages of CD25+ T-suppressor cells and B1a B-cells in the superficial cervical lymph nodes of the asbestos-instilled mice. These data demonstrate that asbestos leads to immunologic changes consistent with the development of autoimmunity. This study provides a non-autoimmune prone murine model for use in future elucidation of mechanisms involved in asbestos-induced autoimmune disease.     

Bimodal effect of amphetamine on motor behaviors in C57BL/6 mice

Amphetamine-induced motor behaviors, i.e., locomotor and stereotypic activities, were simultaneously characterized in C57BL/6 mice, a strain commonly used for genetic studies. Our findings show relatively high levels of focused activities in drug-naive C57BL/6 mice, confirming the lively nature of this mouse strain. Acute amphetamine induced a dose-dependent, bimodal response: locomotion predominated at lower doses of amphetamine and was gradually displaced by stereotypic behavior as dose and time increased. The sum total of both behavioral activities increased with amphetamine dose, supporting the notion that amphetamine-induced locomotion and stereotypy form a continuum. These data provide a basis for using C57BL/6 mice as a strain to study the molecular and cellular mechanisms underlying psychostimulant effects, drug addiction and psychotic disorders.     

四氢大麻酚对C57BL/6小鼠自身免疫性肝炎的保护作用

为研究大麻素成分[四氢大麻酚(tetrahydrocannabinol, THC)]对C57BL/6小鼠自身免疫性肝炎(autoimmune hepatitis, AIH)的影响,尾静脉注射质粒pCYP2D6和pcDNA3.1,腹腔重复注射四氯化碳(carbon tetrachloride, CCl_4)和THC,ELISA检测自身免疫应答程度,微板法检测血清中谷丙转氨酶(alanine aminotransferase, ALT)活性,HE染色检测肝脏炎症反应程度,天狼猩红染色检测肝脏纤维化程度。结果显示,THC对由CCl_4/CYP2D6引起的AIH造成的肝损伤有显著改善,而且对自身免疫应答有显著抑制作用,自身抗体和抗CYP2D6抗体水平显著降低,对于单独由CYP2D6引起的抗CYP2D6抗体能够完全抑制。THC对AIH和肝纤维化也有显著的抑制作用,且THC的抑制作用与其浓度有关。由此THC对由CCl_4/CYP2D6引起的C57BL/6小鼠的AIH有显著抑制作用,并且呈剂量依赖性。由此大麻素类药物THC对AIH可能有保护作用。     

Effects of single episodes of severe stress on the behavior of male and female CBA/Lac and C57BL/6J mice

Experiments were performed to compare the behavior of male and female mice of the inbred strains CBA/Lac and C57BL/6J in the open field test after single episodes of severe stress imposed by forced swimming. Testing was performed 2 h (first test) and one day (second test) after stress. Control animals were intact males and females of these strains, and were also tested in the open field on two sequential days. Both male and female CBA/Lac mice showed increases in the latent period of excursions from the center of the field 2 h after stress. This change persisted to the second test in female CBA/Lac mice. In female C57BL/6J mice, there were changes in four of seven behavioral measures 2 h after stress, though at one day their behavior was as in control individuals. Stress had virtually no effect in males of this strain, only increasing the number of grooming acts in the first test. In addition, detailed analysis of the effects of repeat testing in control and stressed individuals of these mouse strains also revealed interstrain and gender-related differences in the effects of stress. The possible existence of increased basal (trait) and situational (state) anxiety in female C57BL/6J and CBA/Lac mice respectively is discussed. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 92, No. 5, pp. 567–577, May, 2006.     

Social success and voluntary ethanol consumption in mice of C57BL/6J and CBA/Lac strains

Voluntary ethanol (20% solution) consumption in mice of C57BL/6J (C57) and CBA/Lac (CBA) strains with consecutive experience of victories (winners) or defeats (losers) in daily intermale agonistic confrontations were studied. Winners and losers of the CBA strain maintained the ethanol consumption on the same level. Losers of the C57 strain increased the ethanol consumption most dramatically during the second week of testing, while winners of this strain did not change the ethanol intake. The aspiration to the social contact estimated by behavioral activity as a reaction to the other male significantly increased in "drinking" losers of the C57 strain. The influence of heredity and emotional state of animals formed by their social success on voluntary ethanol consumption are discussed.     

Sex differences in the effect of ethanol injection and consumption on brain allopregnanolone levels in C57BL/6 mice

The pharmacological profile of allopregnanolone, a neuroactive steroid that is a potent positive modulator of gamma-aminobutyric acidA (GABAA) receptors, is similar to that of ethanol. Recent findings indicate that acute injection of ethanol increased endogenous allopregnanolone to pharmacologically relevant concentrations in male rats. However, there are no comparable data in mice, nor has the effect of ethanol drinking on endogenous allopregnanolone levels been investigated. Therefore, the present studies measured the effect of ethanol drinking and injection on allopregnanolone levels in male and female C57BL/6 mice. One group was given 17 days of 2-h limited access to a 10% v/v ethanol solution in a preference-drinking paradigm, while another group had access to water only. The ethanol dose consumed in 2 h exceeded 2 g/kg. Then, separate groups of mice were injected with either 2 g/kg ethanol or saline. Mice were killed 30 min after the 2-h drinking session or injection. Blood ethanol concentration was significantly higher in the ethanol-injected versus ethanol-drinking groups, even though the dose was similar. Consumption of ethanol significantly increased brain allopregnanolone levels in male but not female mice, compared with animals drinking water, but did not alter plasma corticosterone levels. In contrast, injection of ethanol did not significantly alter brain allopregnanolone levels in male or female mice and only significantly increased plasma corticosterone levels in the male mice, when compared with saline-injected animals. The sex differences in the effect of ethanol administration on endogenous allopregnanolone levels suggest that the hormonal milieu may impact ethanol's effect on GABAergic neurosteroids. Importantly, these data are the first to report the effect of ethanol drinking on allopregnanolone levels and indicate that ethanol consumption and ethanol injection can produce physiologically relevant allopregnanolone levels in male mice. These results have important implications for studies investigating the potential role of endogenous allopregnanolone levels in modulating susceptibility to ethanol abuse.     

Changes with age in cadmium and copper levels in C57BL/6J mice

Cadmium concentrations in C57BL/6J male mice were found to increase with age in kidney from 0.1 ng/mg dry wt. at 45 days of age to 1.7 ng/mg dry wt. at 880 days of age. Cadmium in liver increased exponentially with age with a doubling time of 242 days, from a value of 0.03 ng/mg dry wt. at 45 days of age to 0.29 ng/mg dry wt. at 880 days of age. Kidney copper declined by only 14% between 45 and 400 days of age and remained unchanged between 400 and 880 days of age. Liver copper declined 41% between 45 and 500 days of age and showed no change between 500 and 880 days of age. Most of the decline in kidney and liver copper concentrations occurred before 240 days of age, possibly reflecting developmental changes. Feeding cadmium chloride in drinking water at concentrations of up to 100 microgram/ml did not change the copper concentrations in kidney, liver, heart or brain of young mice. Feeding copper gluconate did not change the cadmium concentration in livers of old mice. However, these treatments did change the cadmium/copper ratios in tissues.     

Behavioral changes in aging female C57BL/6 mice

Using a range of tests we have studied alterations in behavior with advancing age in female C57BL/6 (of Jackson origin), the golden standard on which most genetically engineered mice are back-crossed. In parallel, growth and survival data were collected. In a protected environment the 90% and 75% cohort survival age was 20 and 25 months, respectively, and the 50% cohort survival was 32 months. In mice, body weight increases continuously until 15-20 months of age, while in advanced age whole body weight drops. The body mass loss in senescence is associated with emergence of other aged phenotype features such as kyphosis, balding and loss of fur-color.Our behavioral data show that aging modulates certain aspects of basic behavior in a continuous manner, like explorative and locomotor activities. Advanced age associates with an acceleration of behavioral impairments evident in most of the tests used, including motor skill acquisition and memory consolidation. However, certain domains of mouse behavior were well preserved also in advanced age such as thermal noxious threshold and working memory as assessed by an object recognition task. The decreased drive to explore is suggested to be a key factor underlying many aspects of reduced performance including cognitive capacity during aging. Behavioral aging affects genetically closely related individuals housed under strictly standardized conditions differentially (Collier, T.J., Coleman, P.D., 1991. Divergence of biological and chronological aging: evidence from rodent studies. Neurobiol. Aging, 12, 685-693; Ingram, D.K., 1988. Motor performance variability during aging in rodents. Assessment of reliability and validity of individual differences. Ann. N.Y. Acad. Sci., 515, 70-96). Consistent with this a subpopulation of the 28-month-old mice showed an explorative activity similar to young-adult mice and a significantly stronger preference for a novel object than aged mice with a less explorative behavior. Thus, subtle environmental factors and epigenetic modifications may be important modulators of aging.     

The superior olivary complex in C57BL/6 mice

The cellular and cytoarchitectural features of the lateral superior olive, the medial superior olive, the superior paraolivary nucleus and the medial, lateral and ventral nuclei of the trapezoid body are described in C57BL/6 mice using Nissl, Bodian and Golgi techniques. Principal, spindle and marginal cells are present in a well-defined lateral superior olive. The dendrites of these cells run primarily within rostrocaudal sheets as in the cat. The principal cells of the medial nucleus of the trapezoid body are similar to the principal cells in the cat. Large multipolar cells characterize the lateral nucleus of the trapezoid body and bipolar cells with a medial-lateral orientation are found in the medial superior olive. The largest neurons are found in the superior paraolivary nucleus and the lateral superior olive, and the medial and ventral nuclei of the trapezoid body. While brain weight and neuronal packing density change with development, the characteristic location of cell groups and the shape and Nissl-staining pattern of neurons in the youngest brains examined were essentially unchanged in the adult mice, although dendritic maturation had occurred. The homologies of the C57BL/6 superior olivary complex nuclei with the same areas described in other mouse strains, rat and cat are discussed. This study expands our understanding of the organization of the superior olivary complex in an inbred strain of Mus musculus and relates it to other species. The data about changes occurring during postnatal maturation may aid in the interpretation of behavioral and physiological studies of neonatal plasticity of the auditory system.     

Nyctohemeral differences in response to restraint stress in CD-1 and C57BL/6 mice

Restraint represents psychological and physical stress. Methods used to model restraint stress in mice vary in duration, time of day during which restraint is applied, and the strain of mouse tested. The goals of this study were: (1) to identify the optimal daily time periods during which the stress response is maximized, and (2) to describe mouse strain differences, if any, in response to restraint. Groups of outbred CD-1 and inbred C57BL/6 mice were restrained for 3 h during three time points of the daily light-dark cycle: (1) the late light phase, (2) the transition between the light phase and the dark phase, and (3) the mid-dark phase. Additional mice served as control groups for food deprivation or were unhandled except for blood sampling. Mice of both strains lost significant body mass after 3 days of restraint. Unrestrained food-deprived mice lost body mass, particularly if food-deprived during transition periods. Corticosterone was elevated in restrained mice compared with control mice. Neither basal nor postrestraint corticosterone differed between strains. Corticosterone was elevated by food deprivation during transitional periods in CD-1 mice and during both transition and dark phases in C57 mice. Corticosterone response in restrained CD-1 mice was increased during the dark phase. These results suggest that the physiological response to restraint is similar in both strains. However, corticosterone responses to both restraint and food deprivation were highest during the transitional and dark phases.     

Variants of secondary immune response in CBA and C57Bl/6 mice

The manifestation of a secondary immune response to intraperitoneal and subcutaneous injection of sheep red cells in various doses was studied in CBA and C57Bl/6 mice. The parameters under study were the delayed-type hypersensitivity reaction and antibody production assessed from the levels of antibody-producing cells of classes M and G in the lymph node and spleen. The manifestation and correlations between delayed-type hypersensitivity and antibody production were found to depend on the route of antigen administration and its first immunizing dose, interval between the two immunizations, and genetic control of the immune response. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 11, pp. 486–488, November, 1994 Presented by K. P. Kashkin, Member of the Russian Academy of Medical Sciences     

免疫重建小鼠抗红白血病的作用研究

目的:观察在免疫重建过程中应用白血病瘤苗对C57BL/6小鼠一般状况、抵御FBL-3细胞攻击及小鼠保护性免疫功能的作用.方法:用同系小鼠脾脏淋巴细胞对照射后的免疫缺陷鼠进行免疫重建,同时用灭活FBL-3细胞皮下注射免疫C57BL/6小鼠,7天后用FBL-3细胞皮下攻击小鼠,观察小鼠的一般状况、成瘤率、瘤块生长情况;通过ELISA法测定外周血IFN-γ含量,以评估细胞免疫作用的强弱;通过病理切片了解瘤块中心及周围细胞浸润情况.结果:免疫重建 瘤苗可以有效提高单纯应用瘤苗所产生的保护性免疫功能,IFN-γ含量明显升高;用FBL-3细胞攻击,成瘤小鼠瘤块生长缓慢,瘤周单个核细胞浸润明显,瘤块内肿瘤细胞坏死明显,生存期明显延长.结论:在免疫重建的同时应用瘤苗,可以加强瘤苗的保护性免疫作用,为临床应用瘤苗治疗时机提供实验依据.     

硫辛酸改善高脂小鼠氧化应激和慢性炎症的研究

目的:探讨由长期喂饲高脂引发的小鼠机体氧化应激对细胞因子的分泌以及炎症相关基因表达的影响,评价通过添加抗氧化剂硫辛酸对长期氧化应激和慢性炎症的改善作用。方法:30只C57BL/6雄性小鼠,随机分为3组:对照组,高脂模型组(HFD),硫辛酸组(LA)。喂饲10周后测定血浆和脾脏的氧化应激指标。酶联免疫法检测血浆中IFN-γ、IL-4、IL-6、TNF-α、IL-10的含量。荧光定量PCR检测脾脏炎症相关基因C-Jun、NF-κB以及与抗氧化相关基因Mt-1的表达。结果:长期高脂喂饲可导致小鼠免疫器官抗氧化酶活性显著降低,MDA含量显著升高,形成氧化应激。机体长期处于氧化应激态可使血浆IL-4和IL-10显著降低,IFN-γ、IL-6和TNF-α水平显著升高,同时C-Jun和NF-κB炎症反应相关基因表达上调、Mt-1的表达水平下调。添加0.1%LA可有效地防止机体氧化应激的形成。结论:长期高脂喂饲导致的氧化应激可影响机体的免疫功能并诱发慢性炎症反应,LA通过直接清除自由基、恢复氧化还原平衡解除慢性氧化应激从而保护小鼠的免疫功能免受损伤。     

Effect of dalargin on cell multiplication in the gastric epithelium during stress

Central Research Laboratory, Khabarovsk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR, A. D. Ado.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 10, pp. 399–401, October, 1990.