Naloxone Effects on Behavior of Inbred Mice with Different Response to Emotional Stress in Open Field Test

Effects of nonspecific opiate receptor antagonist naloxone in doses of 0.1, 0.5, 1.0, 5.0, 10.0 mg/kg on open field behavior and spontaneous motor activity were studied in male BALB/c and С57Bl/6 mice. Differently directed effects of naloxone on behavioral parameters of emotional-stress reaction in BALB/c and С57Bl/6 mice were observed. Naloxone increased motor activity in the open field test in BALB/c mice, but decreased it in С57Bl/6 mice. In the absence of stress, naloxone in the studied dose range did not affect spontaneous motor activity in С57Bl/6 mice, and significantly reduced activity in BALB/c mice in doses 0.5 and 1.0 mg/kg.     

Beneficial Effect of Eucommia Polysaccharides on Systemic Lupus Erythematosus-like Syndrome Induced by Campylobacter jejuni in BALB/c Mice

The stem bark of Eucommia ulmoides Oliv. is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia in traditional Chinese medicine. This study was to determine whether the crude polysaccharides (EUPs) isolated from the stem bark of E. ulmoides had beneficial effects on lupus-like syndrome in mice. BALB/c mice were immunized with CJ-S₁₃₁ in Freund’s complete adjuvant on day 0, and then boosted on day 14. EUPs 15 or 30 mg kg⁻¹·day⁻¹, or prednisone 5 mg kg⁻¹·day⁻¹ was given to BALB/c mice intragastrically from day 0 to 34. Treatment with EUPs 15 or 30 mg kg⁻¹·day⁻¹ for 35 days protected kidney from glomerular injury with reduced immunoglobulin deposition and lowered proteinuria. The increased production of serum autoantibodies and total immunoglobulin G (IgG) was also inhibited. These findings suggested that Eucommia polysaccharides had a beneficial effect on systemic lupus erythematosus-like syndrome induced by CJ-S₁₃₁ in BALB/c mice.     

Definition of an epitope on Japanese encephalitis virus (JEV) envelope protein recognized by JEV-specific murine CD8+ cytotoxic T lymphocytes

Summary.  We defined an epitope on the Japanese encephalitis virus (JEV) envelope (E) protein recognized by CD8⁺ cytotoxic T lymphocytes (CTLs). CTLs induced in JEV-infected BALB/c (H-2^d) mice recognized E and/or premembrane (PrM) proteins, while CTLs in C57BL/6J (H-2^b) and C3H/HeJ (H-2^k) mice did not. JEV-specific CTLs had a phenotype of CD3⁺ CD4⁻ CD8⁺. Twenty-four 9-amino acid (a.a.) peptides, which had binding motifs for H-2K^d, H-2L^d or H-2D^d, were synthesized according to the amino acid sequences of PrM and E proteins. CTLs induced by JEV infection recognized only the peptide K-3. Immunization of BALB/c mice with only a group of peptides including K-3 induced CTLs which recognized the homologous K-3 peptide, while immunization with other peptides did not. The peptide K-3 had a binding motif for H-2K^d. This is consistent with the finding that JEV-specific CTLs in BALB/c mice was H-2K^d-restricted. These results indicate that the epitope recognized by CTLs in BALB/c mice is located between a.a. 60 and 68 on the E protein, corresponding to an a.a. sequence of CYHASVTDI. Accepted September 29, 1999     

Multidimensional assessment of differences in monoamine metabolism in C57Bl/6 and BALB/c mice

Monoamine metabolism in the hypothalamus and striatum of BALB/c and C57Bl/6 mice (intact and stressed in the open field test) was studied using single-and multidimensional statistical methods. It is suggested that the revealed difference in neurotransmitter metabolism is associated with genetically controlled behavior of these animals under conditions of emotional stress. The results of discriminant analysis suggest that the regulation of monoamine metabolism during emotional stress is genetically determined. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 5, pp. 574–577, May, 2000     

Immune response and inhibitory effect of ketotifen on the BALB/c and C3H/HeN mice infected with <Emphasis Type="Italic">Echinostoma hortense</Emphasis>

Although Echinostoma hortense is one of the intestinal trematodes with a high infection rate in South Korea, the exact immune response against E. hortense infection has yet to be fully investigated. In the present study, we investigated differential susceptibilities in two different strains of micenamely, BALB/c (H-2d) and C3H/HeN (H-2k) mice. Likewise, we investigated the effects of ketotifen, an antiallergic drug, on the immune response against E. hortense infection. The worm recovery rate of the C3H/HeN mice was much higher than that of the BALB/c mice. The messenger ribonucleic acid (mRNA) expressions of interleukin (IL)-4 and IL-5 in the BALB/c mice were stronger than that of the C3H/HeN mice after E. hortense infection, but IL-1β and tumor necrosis factor (TNF)-α expressions in the BALB/c mice were weaker than that of the C3H/HeN mice after E. hortense infection. The number of goblet cells and eosinophils increased after E. hortense infection in the BALB/c and the C3H/HeN mice. The worm recovery rate was higher and lasted longer in the ketotifen-treated mice in comparison to the untreated mice. Ketotifen suppressed the mRNA expression of IL-4 and IL-5 in the BALB/c mice, but did not in the C3H/HeN mice. The IL-1β expressions were inhibited by ketotifen in the two strains, but TNF-α expression was inhibited in the C3H/HeN mice after ketotifen treatment. In addition, ketotifen inhibited the increase in eosinophils and goblet cells in varying degrees, depending on the strain. In summary, the immune sensitivity against E. hortense depends on the species of the host. The ketotifen treatment administered on the infected mice differently blocked the immune response against E. hortense infection.     

Evidence for a supportive role of classical transient receptor potential 6 (TRPC6) in the exploration behavior of mice

Non-selective classical transient receptor potential (TRPC) cation channels share important roles in processes of neuronal development and function. To test the influence of TRPC6 activity on behavior, we developed a TRPC6-deficient (TRPC6^−/−) mouse model in a BALB/c genetic background. Both, TRPC6^−/− and wild-type (WT) mice were analyzed first for their general health and reflex status (modified SHIRPA protocol) and then in three different behavioral tests (marble-burying test, square open field and elevated star maze). No abnormalities were detected in the SHIRPA protocol. Most interestingly, TRPC6^−/− mice showed no significant differences in anxiety in a marble-burying test, but demonstrated reduced exploration in the square open field and the elevated star maze. Therefore, TRPC6 channel activity may play a yet unknown role for exploration behavior.     

Psychotropic Effects of Sidnocarb and Ladasten in Inbred Mice with Different Reaction to Emotional Stress

Dose-dependent relationship of the effects of sidnocarb and Ladasten on open field behavior and free motor activity was studied in inbred C57Bl/6 and BALB/c mice differing by emotional stress reaction phenotype. Ladasten in a dose of 10 mg/kg produced activating and anxiolytic effects on BALB/c mice in the open field test. Combined injection of Ladasten (10 mg/kg) and sidnocarb (6 or 12 mg/kg) activated animal behavior in both tests.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 3, pp. 316–318, March, 2005     

Increased Resistance to Staphylococcus aureus Endophthalmitis in BALB/c Mice: Fas Ligand Is Required for Resolution of Inflammation but Not for Bacterial Clearance

FasL was recently shown be required for bacterial clearance in C57BL/6 mice that express the FasL.1 allotype. The FasL.2 allotype is expressed in BALB/c mice and exhibits increased binding affinity to and increased cytotoxic activity against Fas⁺ target cells. Therefore, we hypothesized that BALB/c mice would be more resistant to Staphylococcus aureus-induced endophthalmitis. To test this hypothesis, C57BL/6, BALB/c, and BALB(gld) mice received intravitreal injections of 2,500 CFU of S. aureus (RN6390). Clinical examinations, electroretinography (ERG), histology, and bacterial quantification were performed at 24, 48, 72, and 96 h postinjection. The myeloperoxidase (MPO) assay was used to quantitate neutrophil infiltration. At 96 h postinfection, 86% of C57BL/6 mice presented with complete destruction of the eye, compared to only 29% of BALB/c mice with complete destruction. To our surprise, in the absence of Fas ligand, BALB(gld) mice showed no difference in bacterial clearance compared to BALB/c mice. However, histology and ERG analysis revealed increased retinal damage and significant loss of retinal function. MPO analysis revealed equal numbers of neutrophils in BALB(gld) and BALB/c mice at 24 h postinfection. However, at 48 h, the neutrophil numbers remained significantly elevated in BALB(gld) mice, correlating with the increased retinal damage observed in BALB(gld) mice. We conclude that the increased resistance to S. aureus induced endophthalmitis in BALB/c mice is not dependent upon the FasL. However, in contrast to C57BL/6 mice, FasL is required for resolution of inflammation and protecting host tissue from nonspecific damage in BALB/c mice.     

B-cell activation in the mesenteric lymph nodes of resistant BALB/c mice infected with the murine nematode parasite Trichuris muris

Immune responses in resistant BALB/c mice infected with the murine nematode parasite Trichuris muris were examined. Following the establishment of infection, worm burdens of T. muris were expelled by BALB/c mice by day 21 postinfection (p.i.). Specific immunoglobulin G₁ (IgG₁) antibodies to T. muris excretory/secretory (E/S) antigens were detected in sera from infected mice, though specific IgG_2a antibodies were not observed during infection. Ig-producing cells increased in the mesenteric lymph nodes (MLN) of infected mice on days 7, 14, and 21 p.i., with the greatest increase in numbers of IgG- and IgA-producing cells occurring on day 14. Marked increases in the relative percentages of B220⁺ and surface Ig⁺ (sIg⁺) cells were observed in the MLN of infected mice on days 14 and 21 p.i. Furthermore, cellular expansion of the MLN in infected mice resulted in an increase in the absolute numbers of B220⁺ and sIg⁺ cells. The levels of interleukin 2 (IL-2), IL-4, and interferon-γ (IFN-γ) detected in the supernatants from concanavalin A-stimulated MLN cells of infected mice were higher than those found in normal mice. Consequently, the expulsion of T. muris in resistant BALB/c mice was concomitant with cytokine production and B-cell activation in the MLN of infected mice. These results suggest the involvement of B-cell responses in protective immunity to T. muris infection. Received: 12 May 1998 / Accepted: 5 August 1998     

Morphofunctional characteristic of mast cells in BALB/c and C57Bl/6 mice during cold exposure

Mast cells of the mesentery and subcutaneous tissue in BALB/c and C57Bl/6 mice were studied after single and repeated cold exposure (−20°C, 3 min). Immediate adaptive reactions of mast cells in BALB/c and C57Bl/6 mice did not differ after single cold exposure and were manifested in increased degranulation. Repeated cold exposure of BALB/c mice was followed by an adaptive reaction, which included an increase in the count of mast cells in subcutaneous tissue and normalization of the degranulation index. In C57Bl/6 mice the count of mast cells in subcutaneous tissue decreased, while the degranulation index remained high. These changes reflect the disadaptive response of mast cells to repeated cold exposure. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 8, pp. 207–209, August, 2004     

The role of CD4+ and CD8+ T-cells in host morbidity and innate resistance to Angiostrongylus cantonensis in the mouse

Strain-dependent differences in host morbidity and mortality due to Angiostrongyluscantonensis infection have been established between C57BL/6 and BALB/c mice; C57BL/6 mice show rapid worm killing with low morbidity, whereas BALB/c mice indicate slow worm killing with high morbidity and mortality. To determine the possible roles of CD4⁺ and CD8⁺ T-cells in host morbidity and innate resistance to A. cantonensis infection we treated C57BL/6 and BALB/c mice with anti-CD4 or anti-CD8 monoclonal antibody and examined the changes in host morbidity and worm-killing activity. Our study indicates that anti-CD4 antibody treatment interferes with worm killing and improves the morbidity of A. cantonensis-infected BALB/c mice, whereas anti-CD8 antibody treatment fails to improve the morbidity. Tumor necrosis factor-α (TNF-α, or cachectin) production in infected mice was not correlated with host morbidity. Anti-IL-5 monoclonal antibody treatment also failed to affect the morbidity of infected BALB/c mice, although their worm-killing activity was restrained as shown in anti-CD4-treated mice. These findings clearly indicate that the morbidity of infected BALB/c mice is regulated by some unknown CD4⁺ T-cell-dependent mechanism but not by an IL-5-, eosinophil-, or TNF-α-dependent mechanism. Received: 9 June 1997 / Accepted: 11 July 1997     

Analysis of bromantane pharmacological spectrum

Bromantane (2[n-bromphenyl]aminoadamantane) in doses of 40–60 mg/kg had no effect on spontaneous motor activity of BALB/c mice in a Optovarimex apparatus and prevented freezing in the open field test, but stimulated motor activity in C57B1/6 mice. It is concluded that psychostimulatory and anxiolytic effects are present in the spectrum of the pharmacological activity of bromantane. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 11, pp. 529–531, November, 1999     

Differential immune profiles following experimental Echinostoma hortense infection in BALB/c and C3H/HeN mice

Despite the increasing incidence in food-borne Echinostoma hortense infection, the underlying immune mechanism along with the clinical manifestations and the expulsion of the worms from the mucosal surfaces are not well understood. To clarify the differences in the immune mechanisms induced by E. hortense in the host, we examined the interleukin (IL)-4, IL-5, IL-12, and interferon-γ profiles and the kinetics in two genetically different mouse strains, BALB/c and C3H/HeN mice, in vivo as well as in vitro. Both the crude extract and the excretory–secretory protein prepared from E. hortense increased the mRNA and protein expressions of IL-4 and IL-5 in the splenocytes isolated from both strains of infected mice. The E. hortense recovery rate of the C3H/HeN mice was much higher than that of the BALB/c mice. When analyzing the sera from the infected BALB/c and C3H/HeN mice, the IL-5 and immunoglobulin (Ig)G1 levels in the infected BALB/c mice were significantly higher than those from the C3H/HeN mice (p < 0.05). Taken together, these results show that the BLAB/c mice with E. hortense infection are more resistant than are the C3H/HeN mice due to the significantly higher induction of protective Th2 immunity.     

Cryptosporidium infection in major histocompatibility complex congeneic strains of mice: variation in susceptibility and the role of T-cell cytokine responses

Studies with murine infection models have shown that immunity to the protozoan parasite Cryptosporidium involves T-cells and interferon-gamma (IFN-γ) activity. The present study was performed to compare the course of infection of Cryptosporidium muris in major histocompatibility complex (MHC) congeneic strains of mice and examine the relationship between susceptibility to infection and production of T-cell cytokines. In experiments with BALB mice, the BALB/c strain (H-2 ^d) produced significantly fewer oocysts and recovered from infection sooner than the BALB/B (H-2 ^b) or BALB/K (H-2 ^k) strains. BALB/B X BALB/c F1 hybrid mice were found to express the more susceptible phenotype of the BALB/B parent strain, indicating that the gene(s) in the H-2 locus conferring increased susceptibility to C. muris infection was dominant. At different times during infection of the resistant BALB/c strain and the susceptible BALB/B strain, splenocytes were cultured with soluble parasite antigen and measurements were made of production of a number of T-cell cytokines. Similar patterns of increasing levels of IFN-γ and interleukin 2 (IL-2) were observed in both the resistant and susceptible strains during the patent stage of infection, indicating that production of these type 1 T-helper-cell (TH1) cytokines (i.e. involved in cell-mediated responses) correlated with the development of immunity. This also suggested that the increased susceptibility of BALB/B mice was not associated with a defective TH1 cytokine response. In the study of TH2 cytokines (involved in induction of an antibody response), low levels of IL-10 were detected during infection of BALB/c and BALB/B mice. In contrast, although IL-4 was released by splenocytes of both strains, significantly larger amounts were obtained from cells of the susceptible BALB/B mice in the early stages of infection. Thus, the H-2-dependent variation in susceptibility to infection between these BALB strains correlated with a difference in the pattern of IL-4 secretion. Received: 11 July 1996 / Accepted: 15 September 1996     

Features of the Genetically Defined Anxiety in Mice

The behaviors of male mice of the C57BL/6J (C57), CBA/Lac (CBA) and BALB/c (BALB) strains have been studied in the plus-maze and open field tests for estimation of state anxiety in the stressful novel conditions, and in the cubic box test (exploration of novel cubic box) and the partition test (behavioral reactivity to the unfamiliar partner in the neighboring compartment) for estimation of trait anxiety in the unstressful familiar conditions of the home cage. Plus-maze data suggest that C57 mice are the more anxious than CBA and BALB ones. However, it was revealed the opposite rank order in the open field. The study on the effect of pre-testing in the one of test on the behavior in the other test revealed active behavioral strategy in C57 mice in any situations. The plus-maze behavior of CBA mice was affected to a much lesser extent than in C57 ones after pre-testing in the open field, but expressed changes were observed in open field behavior of CBA mice after pre-testing in the plus-maze. BALB mice displayed low-reactive behavior after any pre-testing exposure under the state anxiety-provoking conditions. Familiar environment revealed a higher level of trait anxiety in C57 than males of other two strains: CBA and BALB mice willingly explore unfamiliar partner and cubic box while C57 mice avoid its. Mainly genetically inherent state anxiety in CBA mice and trait anxiety in C57 mice has been suggested. Lowest state and trait indices of anxiety were revealed in BALB mice in these conditions.     

Antioxidant enzymes and lipid peroxidation in C57Bl/6 and BALB/c mice

Superoxide dismutase and catalase activities and levels of thiobarbituric acid-reactive lipid peroxidation (LPO) products were estimated in the liver of C57B1/6 and BALB/c mice. The results indicate that although antioxidant enzymes are more active in BALB/c mice, compensation of oxidation processes in this strain is possible only if LPO-inducing agents are absent or present at low levels, and that these agents, including exogenous ones, may be expected to activate lipid oxidation in this strain to a greater extent than in C57Bl/6 mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 580–583, December, 1995     

Different susceptibility to 1-methyl-4-phenylpyridium (MPP+)-induced nigro-striatal dopaminergic cell loss between C57BL/6 and BALB/c mice is not related to the difference of monoamine oxidase-B (MAO-B)

Subcutaneous and intraperitoneal administrations of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induce selective dopaminergic (DA-ergic) neuronal death in many animal species. After passing through the blood–brain barrier (BBB), MPTP is converted to 1-methy-4-phenylpiridinium (MPP⁺) by astrocytic monoamine oxidase-B (MAO-B). MPP⁺ then induces the dopaminergic neuronal death. In mice, marked strain differences in the susceptibility to MPTP-injection have been reported. To clarify which factor(s) cause the strain differences, MPTP or MPP⁺ was intracerebroventricularly (icv) injected into adult C57BL/6 (highly susceptible to MPTP) and BALB/c (resistant to MPTP) mice. The brain tissues including the striatum and substantia nigra pars compacta (SNpc) were examined immunohistochemically using an antibody to tyrosine hydrocyrase (TH). MPP⁺-injected C57BL/6 mice showed a significant decrease in TH-immunopositive areas in the striatum at Day 3 post injection (p < 0.01), and TH-positive cells in the SNpc at Days 1 and 3 (p < 0.01), respectively, compared to saline-injected control mice. In addition, MPP⁺-injected BALB/c mice showed a significant decrease in TH-positive areas in the striatum at Days 1 and 3, and SNpc TH-positive cells in the SNpc at Day 3, respectively (p < 0.05). However, the decrease rates in the BALB/c mice were lower than that in C57BL/6 mice. MPTP-injected C57BL/6 mice, however, showed no lesions in the striatum and SNpc at Days 1 and 7 after icv injection. All the present findings indicate that factors other than MAO-B can influence the strain susceptibility between C57BL/6 and BALB/c mice after the conversion from MPTP to MPP⁺.     

The Xid defect determines an improved clinical course of murine leishmaniasis in susceptible mice

The course ofLeishmania majorinfection in B cell-defective BALB.Xidmice was investigated. Infected BALB.Xid mice showed a significantiyslower lesion development compared with BALB/c controls accompaniedby a 10– to 30– fold lower parasite burden in lymphaticorgans. The B cell immune response, as quantified by anti-leishmanialantibody production and B cell numbers in lymphatic organs,remained significantly lower in BALB.Xid mice as compared withBALB/c control mice. In accordance with disease development,CD4⁺ T cells from lymph nodes of infected BALB.Xid mice produced6– to 10– fold more IFN-; than the respective Tcells of BALB/c mice, when stimulated with leishmanial antigeninvitro. B cells from lymph nodes and the peritoneal cavitiesof BALB/c mice could be induced to produce 3– to 8–fold more IL-10 than the respective cells from B cell-defectiveBALB.Xid mice. The data thus indicate that the Xid mutationallows for the development of T_h1 cells which confer resistanceto infection withL. major. Moreover, the data suggest that Bcells contribute to susceptibility to L. major infection inBALB/c mice by skewing the T_h cell network towards a T_h2 phenotype.Since the difference in B cell-derived IL–10 productionbetween BALB/c and BALB.Xid mice was more prominent in peritonealB cells, the data support the notion that the skewing of theT cell response may be predominantly mediated by the B1 cellsubset.