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.     

A deficiency of axonal regeneration in C57BL/6J mice

Axonal regeneration within peripheral nerves and dorsal spinal roots was investigated in inbred strains of mice with known differences in macrophage recruitment and inflammatory functions. During the second week after sciatic nerve crush, counts of regenerating newly myelinated fibres were significantly lower in C57BL/6J mice than in 4 other strains. After dorsal root crush with or without concomitant sciatic nerve transection to enhance regeneration, fibre counts in roots of C57BL/6J were one-fifth of those in A/J mice. Axonal regeneration is subnormal in C57BL/6J mice but this defect appears not to be linked to known deficiencies in macrophage function.     

Studies of axonal regeneration in C57BL/6J and A/J mice

The genetic and biological nature of a deficiency in axonal regeneration in C57BL/6J mice was investigated. From analysis of recombinant inbred strains, the genetic basis for the deficient regeneration behaviours of C57BL/6J and A/J mice is deduced to involve multiple loci. The defect in axonal regeneration in C57BL/6J mice appears to be a delay rather than permanant impairment and appears to involve sensory more than motor axons.     

Macrophage participation in influenza-induced sleep enhancement in C57BL/6J mice

Mice develop changes in sleep during the nonspecific immune response that occurs during the initial few days after inoculation with influenza virus. T lymphocytes, neutrophils, macrophages, and natural killer (NK) cells all participate in the early host response to influenza infection. All of these cell types are potential sources of endogenous substances that modulate sleep, but the contributory role of each cell type to the alteration of somnolence during infection has not been determined. To investigate which cell types contribute to the sleep enhancement that develops during influenza infection in mice, the sleep patterns of C57BL/6J mice with perturbations of particular facets of host immune response capabilities were assessed before and after influenza infection. Targeted mutation of the gene Ccl3 (macrophage inflammatory protein 1 alpha) prevented development of the dark phase sleep enhancement that is characteristic of C57BL/6J mice after influenza infection. Other experimental treatments that impair macrophage or monocyte function also produced significant (administration of pentoxifylline or CNI-1493) or marginally significant (deletion of the interferon-gamma gene or intranasal administration of carrageenan) changes in influenza-induced sleep enhancement in C57BL/6J mice. In contrast, functional impairments of NK cells, neutrophils, and T lymphocytes did not significantly influence sleep responses. These data therefore support a contributory role for macrophages, but not for NK cells, neutrophils, and T lymphocytes, in eliciting the sleep response typical of influenza-infected C57BL/6J mice.     

Morphine-induced activity attenuates phase shifts to light in C57BL/6J mice.

Circadian rhythms can be phase shifted and entrained by daily schedules of light and by non-photic stimuli such as locomotor activity. Relatively little is known of how photic and non-photic stimuli interact to regulate circadian phase. Morphine injections were used to examine the effects of locomotor activity on phase shifts to light pulses in mice free-running in constant dark. Morphine injections scheduled early or late in the active period (subjective night) induced hyperactivity, but did not induce phase shifts. Light pulses late in the subjective night induced phase advance shifts that were significantly attenuated (63% smaller, p<0. 01) by pretreatment with morphine. This inhibitory effect of morphine on light-induced phase advances was blocked by preventing mice from running for 6 h after the injections. Light pulses early in the subjective night induced phase delay shifts that were only weakly attenuated (15% smaller, p=0.06) by morphine. These results demonstrate behavioral inhibition of light-induced phase resetting of circadian rhythms in mice, and suggest that the strength of this effect may be phase dependent, although other interpretations are possible.     

Antidepressant-like effects of ceftriaxone in male C57BL/6J mice.

BACKGROUND: Excessive glutamatergic neurotransmission is hypothesized to be associated with depressive-like behaviors and possibly major depressive disorder (MDD). Recent evidence that beta-lactam antibiotic agents stimulate uptake of glutamate suggests that this class of compounds might possess antidepressant-like activity. METHODS: Three-month old, male, C57BL/6J mice were administered ceftriaxone (200 mg/kg IP) for 14-18 days, then tested in the tail-suspension, forced swim, and novelty-suppressed feeding tests to determine whether ceftriaxone had similar effects to classical antidepressant compounds in these models. RESULTS: Ceftriaxone treatment had an antidepressant-like effect across models. Reduced immobility and decreased freezing were observed in the forced swim and tail suspension tests. The same trend was seen in novelty-suppressed feeding, but the effect was not statistically significant. CONCLUSION: Ceftriaxone demonstrates antidepressant-like effects in several mouse models. This is consistent with the hypothesis that enhanced uptake of glutamate might have antidepressant-like effects.     

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.     

Increased cerebral cortical lipid peroxidation and abnormal phospholipids in aged homozygous apoE-deficient C57BL/6J mice.

Aged homozygous apolipoprotein E gene-deficient (apoE -/-) mice have been proposed as an experimental model for the role of human apoE isoforms in Alzheimer's disease (AD). However, results from different laboratories have been in conflict regarding the presence or absence of neurodegeneration in these mice. Moreover, despite apoE being the major lipid trafficking molecule in the central nervous system, there has been no investigation of brain lipid levels in apoE -/- mice. Here we have examined male and female apoE -/- and control mice aged 10 to 12 months, testing the hypothesis that lack of apoE leads to some of the neuropathological changes seen in AD. Our results failed to demonstrate significant neurodegeneration, histopathological changes, or reduction in cerebral cortical synaptophysin in apoE -/- mice. However, we did observe a significant reduction in cerebral cortical phospholipids and their constituent fatty acids, as well as elevated lipid peroxidation products, in apoE -/- mice compared to apoE +/+ mice with the same genetic background. Our results suggest that the brains of aged apoE -/- mice display some of the lipid abnormalities associated with AD; however, these changes alone, at the magnitudes achieved in the apoE -/- mice, do not directly lead to the major neurodegenerative changes of AD.     

Sociability and brain development in BALB/cJ and C57BL/6J mice

Sociability—the tendency to seek social interaction—propels the development of social cognition and social skills, but is disrupted in autism spectrum disorders (ASD). BALB/cJ and C57BL/6J inbred mouse strains are useful models of low and high levels of juvenile sociability, respectively, but the neurobiological and developmental factors that account for the strains’ contrasting sociability levels are largely unknown. We hypothesized that BALB/cJ mice would show increasing sociability with age but that C57BL/6J mice would show high sociability throughout development. We also hypothesized that littermates would resemble one another in sociability more than non-littermates. Finally, we hypothesized that low sociability would be associated with low corpus callosum size and increased brain size in BALB/cJ mice. Separate cohorts of C57BL/6J and BALB/cJ mice were tested for sociability at 19-, 23-, 31-, 42-, or 70-days-of-age, and brain weights and mid-sagittal corpus callosum area were measured. BALB/cJ sociability increased with age, and a strain by age interaction in sociability between 31 and 42 days of age suggested strong effects of puberty on sociability development. Sociability scores clustered according to litter membership in both strains, and perinatal litter size and sex ratio were identified as factors that contributed to this clustering in C57BL/6J, but not BALB/cJ, litters. There was no association between corpus callosum size and sociability, but smaller brains were associated with lower sociability in BALB/cJ mice. The associations reported here will provide directions for future mechanistic studies of sociability development.     

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.     

Immunological consequences of the reversal of social status in C57BL/6J mice

The present study has shown that the immune response can be influenced by the reversal of animal's social status. For this purpose testing of agonistic interactions under the sensory contact conditions was performed for pairs of either aggressive or submissive C57BL/6J male mice with preliminary experience of 10 or 20 daily confrontations. Tests continued for 10 or 20 days, respectively. The reversal of aggressive behavior into submissive one in C57BL/6J mice resulted in immunosuppression only following 20 daily confrontations compared to the controls as well as to aggressive males which did not change their behavior and showed the increased immune response. Despite the fact that previous experience of defeat was associated with a reduced immune reaction, the occurrence of aggressive behavior in formerly submissive mice during 10 or 20 tests of daily confrontations produced immunostimulation. It is suggested that changes in the neurochemical pattern of the brain can be considered as an underlying basis for the linkage between the immune response and specific behavioral profile.     

Behavioural study of the D-galactose induced aging model in C57BL/6J mice

Rodent chronically injected with D-galactose (D-gal) has been used as an animal aging model for brain aging or anti-aging pharmacology research. However, the dosage of D-gal used to establish this model in mice has been reported in a wide range. To study the dose-dependent effect of D-gal on rodent behaviour, we investigated the learning and memory ability of C57BL/6J (C57) mice after 8-week subcutaneous injection of D-gal at different doses by Morris water maze (MWM) and object recognition test (ORT). In addition, locomotor activity test (LAT) was also performed to examine the neuromuscular function. In comparison of vehicle (0.9% saline)-treated mice, D-gal-treated mice at dose of high (200 mg/kg per day) and middle (100 mg/kg per day) doses showed significant longer latency to platform and less target quadrant search time and distance in MWM In ORT, D-gal at high and middle doses reduced the discrimination index (DI) of mice more significantly than low dose (50 mg/kg per day), although all three doses of D-gal reduced the DI of mice significantly. Furthermore, D-gal at high and middle doses significantly decreased locomotor activity of the mice in LAT. Throughout three tests, D-gal induced behavioural impairments in C57 mice at high and middle doses tended to be in the same degree. These results indicate that d-gal can induce the behavioural impairment of C57 mice in a dose-dependent manner from 50 to 100 mg/kg, higher dose than 100 mg/kg cannot further deteriorate its behavioural performance.     

Effect of duration of haloperidol treatment on DA receptor supersensitization in aging C57BL/6J mice

Apomorphine-induced behavior, striatal [3H]spiperone binding, and striatal choline acetyltransferase (ChAT) activity were assessed in 6 1/2, 13, and 27-30 month-old male C57BL/6J mice following 0, 30, 60 or 90 days treatment with the dopaminergic (DA) antagonist haloperidol. Both apomorphine-induced behavior and [3H]spiperone binding (Bmax) increased linearly with duration of haloperidol treatment, with no detectable age difference in the degree of supersensitization, although basal receptor density declined with age. Middle- and old-aged mice showed prolonged stereotypic behavior relative to young mice, suggesting slower apomorphine clearance. No differences in ChAT activity were detected with either age or duration of haloperidol treatment. Although the group means of binding and behavior were highly related, the within group correlations were poor. Overall, the results suggest that aged animals are capable of DA receptor supersensitization when given a sufficient stimulus--in this case, relatively long treatment regimes. Previously reported deficits in neuroleptic-induced supersensitization in old mice may be confined to relatively short treatment periods at low doses.     

Production of antibodies to human factor viii in the ascitic fluid of C57BL/6J mice

A method is described for the production of a murine antiserum to human factor VIII, and the quantitation of factor VIII related antigen using this antiserum. C57BL/6J mice were injected intraperitoneally with a mixture of factor VIII and complete Freund's adjuvant. Ascitic fluid developed after repeated innoculations for seven to eight weeks, and was subsequently tapped. Using this antiserum, factor VIII related antigen was quantitated by immunoelectrophoresis and enzyme immunoassay. This method provides a simple and economical way of producing an antiserum to factor VIII, and may also be applicable to other proteins available in submilligram quantities.     

Allopregnanolone influences the consummatory processes that govern ethanol drinking in C57BL/6J mice

Although systemic allopregnanolone (ALLO; a positive modulator of GABA(A) receptors) has been shown to enhance ethanol-reinforced responding and to modulate drinking patterns in rodents, the effects of centrally administered ALLO on ethanol intake are not known. The current work examined the effects of intracranial ALLO on operant ethanol self-administration in food- and water-satiated mice, with a procedure designed to estimate ALLO's influence on appetitive versus consummatory processes. Male C57BL/6J (B6) mice were trained to press an ethanol-appropriate lever by being reinforced with 30-min of continuous access to a 10% ethanol solution. Following surgical implantation of a guide cannula aimed at the lateral ventricle and subsequent habituation to vehicle infusions, ALLO (50-400 ng; ICV) was delivered immediately prior to session start. ALLO doses of 100 and 400 ng were further evaluated for their effects on locomotor behavior within activity chambers. ALLO selectively modulated ethanol intake patterns associated with the onset and maintenance of self-administration, while leaving appetitive (i.e., ethanol seeking) measures unaltered. The effects of ALLO on drinking patterns were dissociable from changes in locomotor behavior, as evidenced by the absence of ALLO's influence on response frequency and horizontal distance traveled. These findings support the premise that manipulations in brain ALLO levels may influence the regulatory processes governing ethanol consumption.     

Brain plasticity and cognitive functions after ethanol consumption in C57BL/6J mice

Acute or chronic administrations of high doses of ethanol in mice are known to produce severe cognitive deficits linked to hippocampal damage. However, we recently reported that chronic and moderate ethanol intake in C57BL/6J mice induced chromatin remodeling within the Bdnf promoters, leading to both enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis under free-choice protocol. We performed here a series of cellular and behavioral studies to analyze the consequences of these modifications. We showed that a 3-week chronic free-choice ethanol consumption in C57BL/6J mice led to a decrease in DNA methylation of the Bdnf gene within the CA1 and CA3 subfields of the hippocampus, and upregulated hippocampal BDNF signaling pathways mediated by ERK, AKT and CREB. However, this activation did not affect long-term potentiation in the CA1. Conversely, ethanol intake impaired learning and memory capacities analyzed in the contextual fear conditioning test and the novel object recognition task. In addition, ethanol increased behavioral perseveration in the Barnes maze test but did not alter the mouse overall spatial capacities. These data suggested that in conditions of chronic and moderate ethanol intake, the chromatin remodeling leading to BDNF signaling upregulation is probably an adaptive process, engaged via epigenetic regulations, to counteract the cognitive deficits induced by ethanol.     

Fungiform taste bud degeneration in C57BL/6J mice following chorda-lingual nerve transection

Taste buds are dependent on innervation for normal morphology and function. Fungiform taste bud degeneration after chorda tympani nerve injury has been well documented in rats, hamsters, and gerbils. The current study examines fungiform taste bud distribution and structure in adult C57BL/6J mice from both intact taste systems and after unilateral chorda-lingual nerve transection. Fungiform taste buds were visualized and measured with the aid of cytokeratin 8. In control mice, taste buds were smaller and more abundant on the anterior tip (<1 mm) of the tongue. By 5 days after nerve transection taste buds were smaller and fewer on the side of the tongue ipsilateral to the transection and continued to decrease in both size and number until 15 days posttransection. Degenerating fungiform taste buds were smaller due to a loss of taste bud cells rather than changes in taste bud morphology. While almost all taste buds disappeared in more posterior fungiform papillae by 15 days posttransection, the anterior tip of the tongue retained nearly half of its taste buds compared to intact mice. Surviving taste buds could not be explained by an apparent innervation from the remaining intact nerves. Contralateral effects of nerve transection were also observed; taste buds were larger due to an increase in the number of taste bud cells. These data are the first to characterize adult mouse fungiform taste buds and subsequent degeneration after unilateral nerve transection. They provide the basis for more mechanistic studies in which genetically engineered mice can be used.     

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