Developmental vitamin D deficiency alters adult behaviour in 129/SvJ and C57BL/6J mice

Developmental vitamin D (DVD) deficiency has been proposed as an environmental risk factor for a number of brain disorders. The absence of this vitamin during foetal development in the rat is known to alter behaviour in the adult, and many of these alterations are informative with respect to the clinical features of schizophrenia. Here we investigated whether DVD deficiency had a similar effect on 129/SvJ and C57BL/6J mice. Female mice were fed a diet deficient in vitamin D for 6 weeks prior to conception until birth, after which dams and their offspring were fed a normal diet (i.e. containing vitamin D). Control mice were fed a normal diet throughout the experiment. The adult offspring underwent a comprehensive behavioural test battery at 10 weeks of age. We found that DVD-deficient mice of both strains exhibited significantly higher levels of exploration, as measured by the frequency of head dipping on the hole board test. In addition, DVD-deficient 129/SvJ mice, but not C57BL/6J mice, displayed spontaneous hyperlocomotion. There was no effect of maternal diet on parameters assessed by the SHIRPA primary screen, or on tests of sensorimotor gating, social behaviour, anxiety or depression. Some of these findings resemble the rat phenotype (hyperlocomotion) but there are also novel effects of DVD deficiency on mouse behaviour (increased exploration). This study confirms that the developmental absence of this vitamin affects brain function in another species (mouse), and lends further weight to the hypothesis that DVD deficiency in humans may contribute to adverse neuropsychiatric outcomes.     

A comparison of the behavior of C57BL/6 and C57BL/10 mice

Selection of an appropriate animal model is a crucial first step in many research programs. The C57BL/6 (B6) mouse is the most widely used inbred mouse strain in biomedical research; this is particularly so in behavioral studies. However, there are several C57BL substrains, all derived from common ancestors. C57BL/10 (B10) mice are superficially almost identical to B6 mice in appearance and behavior and widely used in inflammation and immunology research, yet rarely in behavioral studies. The present study assessed the comparability of behavioral results from these two strains, to determine whether they could be used interchangeably in future behavioral experiments. The results showed that the behavior of B6 mice clearly differed from that of B10 mice: in tests of cognition, species-typical behaviors, and motor coordination the B6 strain performed better. Consequently, B6 mice will probably remain the preferred choice for behavioral studies. Interpretation of results derived from the B10 strain should take into account its particular behavioral characteristics.     

Observational learning in C57BL/6j mice

The ability of mice to solve a complex task by observational learning was investigated with C57BL/6j mice. Four female demonstrators were trained to reliably perform a sequence that consisted in pushing a piece of food into a tube attached to the side of a puzzle box, and recovering it by opening a drawer in front of the box. They then performed this sequence in front of naive mice assigned to individual cubicles in a box with a wire mesh front arranged in a row facing the demonstrators. A total of 25 naive mice (13 males and 12 females) were used. Fifteen mice observed 14 demonstrations a day for 5 days; 10 control mice were placed in similar cubicles, but behind a plastic screen which prevented them from observing the demonstrators. The mice were post-tested in the demonstrator situation, and 6 of 15 observers immediately reproduced the complete task successfully, but none of the naive or control mice were able to solve the task. The observers and controls were then subjected to a five level individual learning schedule. Observers learned the individual task significantly faster than the controls. No sex difference was found. These results suggest that observational learning processes at work were based on stimulus enhancement and observational conditioning.     

Comparison of nicotine oral consumption and baseline anxiety measures in adolescent and adult C57BL/6J and C3H/Ibg mice

Approximately 80% of smokers initiate tobacco use during adolescence, suggesting that nicotine initiation and nicotine dependence have a substantial age component. There also is a substantial genetic influence on smoking behaviors such as age of initiation and the development of nicotine dependence. The goal of this study was to examine both genetic background and age dependent effects on oral nicotine self-administration and anxiety-like behaviors in mice. Two inbred mouse strains (C3H/Ibg and C57BL/6J) were assessed for oral nicotine preference during early adolescence (postnatal day 24-35), middle adolescence (postnatal day 36-47), late adolescence (postnatal day 48-59), adulthood (postnatal day 60+) and 2 months following their initial exposure to nicotine. Mice also were assessed for innate anxiety using an elevated zero maze to determine if age and/or genetic background influenced anxiety-like behaviors. Results indicated that initial nicotine preference and nicotine preference two months after an initial exposure are both strain and age dependent. Age also had an effect on some baseline anxiety measures but strain differences for most zero maze measures were present throughout all age groups. In general, early adolescent C3H mice exhibited greater nicotine preference while C57 mice displayed greater preference during middle adolescence and upon a second exposure to nicotine. In contrast, C57 mice exhibited reduced anxiety across all ages tested. These studies indicate that genetic background should be considered when evaluating age-dependent effects of drugs of abuse and baseline anxiety-like behaviors.     

Anxiety-related behaviour in C57BL/6 <--> BALB/c chimeric mice

In a previous study on anxiety-related behaviours of the genetically and behaviourally distant inbred mouse strains C57BL/6 and BALB/c using the Elevated plus-maze (EPM) and Open-field (OF) apparatuses, we identified a number of variables, the factorial scores of which were grouped by principal component analysis (PCA) into factors specifically describing each inbred strain [4]. We have now studied the effect of C57BL/6 and BALB/c haploid sets of genes on this behaviour by comparing EPM and OF variables of C57BL/6 and BALB/c versus C57BL/6×BALB/c F1 hybrids (B6CBF1) and chimeric C57BL/6×BALB/c (CHIM) mice. CHIM mice were made by embryo aggregation and the chimerism degree of their brain was inferred from coat black/white distribution. Discriminant analysis of EPM and OF factorial scores of C57BL/6, BALB/c and CHIM mice showed that CHIM mice with an exceeding (≥80%) C57BL/6 or BALB/c coat component had behaviours similar to those of the predominant strain, whereas CHIM mice with intermediate chimerism differed from both inbred strains. Additional MANOVA analysis showed that the anxiety behaviour of CHIM mice with intermediate chimerism was similar to that of B6CBF1 mice as for factors not describing the inbred strains, including a motor activity mostly limited to protected areas, with attempts to approach the anxiogenic areas while processing/storing the external information. We conclude that the balanced presence of both C57BL/6 and BALB/c genetic backgrounds, either when carried by the same cell or by different cells, gives rise to a novel stress coping strategy described by factors different from those of the inbred strains.     

抑制雌激素的生物合成会引起C57BL/6J卵巢摘除小鼠的轻微焦虑样行为(英文)

目的来曲唑作为新一代芳香化酶抑制剂已广泛用于治疗妇女绝经后的乳腺癌。虽然来曲唑治疗具有良好的耐受性,但其对中枢神经系统的副作用还需要更多的研究。方法将卵巢摘除的C57BL/6J雌性小鼠每天给予来曲唑(2.5mg/kg)或赋形剂灌胃处理,共持续3周。给药结束后,对小鼠自主运动、探索、焦虑、抑郁以及学习和记忆行为进行分析。结果与对照小鼠相比,来曲唑处理小鼠的体重显著增加,海马组织匀浆中的雌激素水平显著降低。旷场实验中,来曲唑处理小鼠在第3天任务中进入旷场中央区域的潜伏期显著增长。高架十字迷宫中,来曲唑处理小鼠在开放臂上运动距离变短。在明暗箱、强迫游泳和Y-迷宫任务中,来曲唑处理小鼠行为未有显著改变。在Morris水迷宫中,来曲唑给药小鼠的空间学习和记忆能力有所提高。结论系统性芳香化酶抑制剂降低了小鼠中枢神经系统中雌激素的含量,并且导致了焦虑样行为的增加,提示使用芳香化酶抑制剂治疗乳腺癌可能对中枢神经系统产生副作用。     

MBP-PLP fusion protein-induced EAE in C57BL/6 mice

Gene knock-out and knock-in mice are becoming increasingly indispensable for mechanism-oriented studies of EAE. Most gene-modified mice are on the C57BL/6 background, for which presently there are only two EAE models available, the MOG peptide 35-55 and the PLP 178-191 peptide induced disease. However, because MS is not a single pathogenic entity, different EAE models are required to reproduce and study its various features. Here we are introducing MBP-PLP fusion protein (MP4)-induced EAE for C57BL/6 mice. B cell- and CD8+ T cell-dependence, as well as multi-determinant recognition are among the unique features of this demyelinating EAE.     

Effects of ethanol on nicotine-induced conditioned place preference in C57BL/6J mice

It has been shown that small doses of ethanol (相似文献   

Effects of repeated fluoxetine and citalopram administration on cytokine release in C57BL/6 mice

This study examines the effects of repeated administration of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram (10 mg/kg, i.p.), on immunoreactivity in C57BL/6 mice. Immune functions were evaluated by the ability of splenocytes to reduce a tetrazolium salt to formazan (MTT test), to proliferate, and to produce cytokines, including interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10 and interferon gamma (IFN gamma). Citalopram administered for 1, 2 and 4 weeks stimulates the proliferative activity of splenocytes and suppresses their ability to secrete the anti-inflammatory cytokine IL-4. Fluoxetine administration for 1 and 2 weeks, but not 4 weeks, stimulates the proliferative activity of splenocytes, whereas a 4-week administration of fluoxetine suppresses the secretion of IL-4. Four weeks of prolonged administration of citalopram and fluoxetine induces a significant increase in the production of IL-6 and IL-10, a cytokine with immunosuppressive and anti-inflammatory activities. The results show that, in C57BL/6 mice, the immunomodulatory effects of SSRIs depend on the SSRI used and the duration of administration.     

Regional neuropathology following kainic acid intoxication in adult and aged C57BL/6J mice

We evaluated regional neuropathological changes in adult and aged male mice treated systemically with kainic acid (KA) in a strain reported to be resistant to excitotoxic neuronal damage, C57BL/6. KA was administered in a single intraperitoneal injection. Adult animals were dosed with 35 mg/kg KA, while aged animals received a dose of 20 mg/kg in order to prevent excessive mortality. At time-points ranging from 12 h to 7 days post-treatment, animals were sacrificed and prepared for histological evaluation utilizing the cupric-silver neurodegeneration stain, immunohistochemistry for GFAP and IgG, and lectin staining. In animals of both ages, KA produced argyrophilia in neurons throughout cortex, hippocampus, thalamus, and amygdala. Semi-quantitative analysis of neuropathology revealed a similar magnitude of damage in animals of both ages, even though aged animals received less toxicant. Additional animals were evaluated for KA-induced reactive gliosis, assayed by an ELISA for GFAP, which revealed a 2-fold elevation in protein levels in adult mice, and a 2.5-fold elevation in aged animals. Histochemical evaluation of GFAP and lectin staining revealed activation of astrocytes and microglia in regions with corresponding argyrophilia. IgG immunostaining revealed a KA-induced breach of the blood-brain barrier in animals of both ages. Our data indicate widespread neurotoxicity following kainic acid treatment in C57BL/6J mice, and reveal increased sensitivity to this excitotoxicant in aged animals.     

氯氮平对雄性小鼠血糖和胰岛素的影响

目的：探讨氯氮平对雄性C57BL／6小鼠血糖和胰岛素的影响。方法：63只雄性C57BL／6小鼠随机分为3大组,空白组、氯氮平4mg／kg组、氯氮平20mg／kg组,于灌药后的3h、1周、4周测定空腹血糖、糖耐量、胰岛素。结果：灌药后3h、l周空腹血糖、血胰岛素、血糖曲线下面积都无显著升高;灌药4周后空腹血糖值显著升高。腹腔注射高糖后60min的氯氮平20mg/kg组的血糖值及血胰岛素显著升高,结诊：氯氮可以慢性升高小鼠的空腹血糖和胰岛素,影响糖耐量,但急性期无明显影响。     

Sexual dimorphic distribution of cannabinoid 1 receptor mRNA in adult C57BL/6J mice

The cannabinoid 1 receptor (CB₁R) is the most abundant G protein-coupled receptor in the brain and plays crucial roles in emotion and behavior by modulating or mediating synaptic transmission and plasticity. Differences in CB₁R density between male and female rodents may be associated with distinct behavioral phenotypes. In the rat brain, CB₁R expression is significantly lower in the prefrontal cortex and amygdala of estrus females than in males. However, differences in CB₁R distribution due to sex over the whole mouse brain are still largely unknown. Here, we systemically investigated the expression of CB₁R mRNA in the brains of both male and female adult C57BL/6J mice using fluorescence in situ hybridization. There were significantly more CB₁R positive cells in males than in females in the orbital cortex, insular cortex, cingulate cortex, piriform cortex, secondary visual cortex, caudate putamen (striatum), and ventral hippocampal CA1. There were significantly more CB₁R mRNA cells in females than males in the fornix and dorsal hypothalamus. However, in some regions, strong hybridization signals without sex differences were detected, such as in the motor cortex, septum, medial habenular nucleus, and inferior colliculus. Moreover, female mice displayed different CB₁R mRNA expression patterns in the medial amygdala, basolateral amygdala, and parabrachial nucleus during different phases of the estrous cycle. These findings provide a basis for understanding sexual dimorphism in physiological and pathological brain functions related to CB₁R.     

Topiramate reduces ethanol consumption by C57BL/6 mice

BACKGROUND: Previous reports indicate that topiramate (TPM) might be an effective treatment for alcohol dependence, perhaps due to a decrease alcohol's rewarding effects resulting from inhibition mesocorticolimbic dopamine (DA) release. Additional reports indicate that TPM antagonizes chronic changes induced by alcohol at the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptors. In the present study, a C57BL/6 (B6) murine model (n = 40) was used to evaluate the effect of TPM on the consumption of 12% alcohol over a 21-h period. METHODS: TPM (0, 10, 30, 90 mg/kg) injected subcutaneously into B6 mice 60 min prior to access to a 12% ethanol solution (v/v) over 8 days produced dose-responsive reduction in consumption during the first 2-h period after injection. RESULTS: Across the 8 days of treatment ethanol intake (g/kg) for SAL, T10, T30, and T90, respectively, was 1.34, 1.03, 0.72, and 0.67. This reduction appears to require systemically available TPM since it was not statistically supported when assessed over the entire 21-h period of ethanol availability. None of the TPM doses affected food consumption or body weight, and T90 dose did not reduce motor activity either by itself or in combination with ethanol. CONCLUSIONS: Unlike previous experiments using the same B6 mouse model to assess naltrexone or tiagabine, there was no evidence that mice developed tolerance to the TPM-induced reductions in ethanol consumption. Thus, in the B6 mouse, TPM reduced ethanol intake at doses with no readily apparent adverse side effects, an effect consistent with recent clinical reports. Additional study will be directed toward characterizing TPM as a treatment for alcohol dependence.     

Tripchlorolide protects against MPTP-induced neurotoxicity in C57BL/6 mice

Many current studies of Parkinson's disease (PD) suggest that inflammation is involved in the neurodegenerative process. Tripchlorolide (TW397), a traditional Chinese herbal compound with anti-inflammatory and immunosuppressive properties, has been shown to protect dopaminergic neurons against, and restore their function after, the neurotoxicity induced by 1-methyl-4-phenylpyridinium ions in vitro. This study was designed to investigate the effect of TW397 in vivo in the PD model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned C57BL/6 mice. In the animals that received vehicle-only (i.e., no TW397) treatment with MPTP i.p. injection, the survival ratios of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra pars compacta and TH-IR fibres in the striatum were only 59 and 13%, respectively, compared with the normal controls. Intriguingly, in conjunction with MPTP, treatment with TW397, 1 microg/kg for 16 days, once per day, dramatically improved the survival rate of the TH-IR neurons and TH-IR fibres to 80 and 43% of the control. The treatment with TW397 also significantly improved the level of dopamine in the substantia nigra and striatum to 157 and 191%, respectively, of the MPTP- plus vehicle-treated group. In addition, in MPTP-treated animals the rota-rod performances of those treated with 0.5 or 1 microg/kg TW397 were significantly improved, by approximately 2- and 3-fold, respectively, relative to vehicle-treated animals. The neuroprotective effect of TW397 was coincident with an attenuated astroglial response within the striatum. These data demonstrate a neuroprotective action of TW397 in vivo against MPTP toxicity, with important implications for the treatment of PD.     

Acetylcholinesterase molecular forms in C57BL/6J dystrophic mice

Acetylcholinesterase (AChE) was extracted from normal and dystrophic C57BL/6J mouse hindlimb muscles and its molecular forms fractionated by sucrose density gradient ultracentrifugation. In the soleus muscles from 6- to 7-week-old mice an increase in the 3 Svedberg unit (S) and a decrease in the 16S AChE molecular forms was observed in dystrophic animals compared to controls. At 12-13 weeks of age, no major significant differences in the relative proportions of AChE molecular forms were noted. In the extensor digitorum longus (EDL) muscles of 6- to 7-week-old dystrophic mice a significant decrease in the proportion of the 10S AChE molecular form and an increase in the 3S and 5S forms was observed. At 12-13 weeks, the dystrophic EDL muscles again displayed a decrease in the 10S form; however, the increase in the 3S and 5S AChE forms, while still apparent, was not significant. These results provide evidence for a biochemical abnormality in the distribution of specific AChE molecular forms, and a differential expression of this abnormality in the soleus and EDL muscles.     

Lesion-induced DA supersensitivity in aging C57BL/6J mice

Lesion-induced dopaminergic supersensitivity was investigated in 4-, 10-, and 28-month-old C57BL/6J mice. Apomorphine-induced rotational behavior was examined 5, 10, and 20 days after destruction of the dopamine-containing nigro-striatal pathway by intrastriatal infusion of 6-OHDA. No major differences between ages were observed in the extent or rate of development of contralateral rotation. It is concluded that age-differences in dopaminergic supersensitization are dependent upon the nature and/or severity of the sensitizing stimulus.     

Effects of chronic swim stress on EtOH-related behaviors in C57BL/6J, DBA/2J and BALB/cByJ mice

There is a strong clinical relationship between stress and stress-related disorders and the incidence of alcohol abuse and alcoholism, and this relationship appears to be partly genetic in origin. There are marked strain differences in ethanol (EtOH)-related behaviors and reactivity to stress, but little investigation of the interaction between the two. The present study assessed the effects of chronic exposure to swim stress on EtOH-related behavior in three common inbred strains of mice, C57BL/6J, DBA/2J and BALB/cByJ. After establishing baseline (10%) EtOH self-administration in a two-bottle free choice test, mice were exposed to daily swim stress for 14 consecutive days and EtOH consumption was measured as a percent of baseline both during stress and for 10 days afterwards. A separate experiment examined the effects of 14 days of swim stress on sensitivity to the sedative/hypnotic effects of an acute injection of 4g/kg EtOH. Results showed that stress produced a significant decrease in EtOH consumption, relative to pre-stress baseline, in DBA/2J and BALB/cByJ, but not C57BL/6J mice. By contrast, stress increased sensitivity to the sedative/hypnotic effects of EtOH in all three strains. These findings demonstrate that chronic swim stress produces reductions in EtOH self-administration in a strain-dependent manner, and that these effects may be restricted to strains with a pre-existing aversion to EtOH. Present data also demonstrates a dissociation between effects of this stressor on EtOH self-administration and sensitivity to EtOH's sedative/hypnotic effects. In conclusion, strain differences, that are likely in large part genetic in nature, modify the effects of this stressor on EtOH's effects in a behavior-specific manner.     

Early postnatal motor experience shapes the motor properties of C57BL/6J adult mice

This study aimed to evaluate the long‐term consequences of early motor training on the muscle phenotype and motor output of middle‐aged C57BL/6J mice. Neonatal mice were subjected to a variety of motor training procedures, for 3 weeks during the period of acquisition of locomotion. These procedures are widely used for motor training in adults; they include enriched environment, forced treadmill, chronic centrifugation, and hindlimb suspension. At 9 months, the mice reared in the enriched environment showed a slower type of fibre in slow muscles and a faster type in fast muscles, improved performance in motor tests, and a modified gait and body posture while walking. The proportion of fibres in the postural muscles of centrifuged mice did not change, but these mice showed improved resistance to fatigue. The suspended mice showed increased persistence of immature hybrid fibres in the tibialis, with a slower shift in the load‐bearing soleus, without any behavioural changes. The forced treadmill was very stressful for the mice, but had limited effects on motor output, although a slower profile was observed in the tibialis. These results support the hypothesis that motor experience during a critical period of motor development shapes muscle phenotype and motor output. The different impacts of the various training procedures suggest that motor performance in adults can be optimized by appropriate training during a defined period of motor development.