Pheromone of grouped female mice impairs genome stability in male mice through stress-mediated pathways.

Population density is known to affect the health and survival of many species, and is especially important for social animals. In mice, living in crowded conditions results in the disruption of social interactions, chronic stress, and immune and reproductive suppression; however, the underlying mechanisms remain unclear. Here, we investigated the role of chemosignals in the regulation of mouse physiology and behavior in response to social crowding. The pheromone 2,5-dimethylpyrazine (2,5-DMP), which is released by female mice in crowded conditions, induced aversion, glucocorticoid elevation and, when chronic, resulted in reproductive and immune suppression. 2,5-DMP olfaction induced genome destabilization in bone marrow cells in a stress-dependent manner, providing a plausible mechanism for crowding-induced immune dysfunction. Interestingly, the genome-destabilizing effect of 2,5-DMP was comparable to a potent mouse stressor (immobilization), and both stressors led to correlated expression changes in genes regulating cellular stress response. Thus, our findings demonstrate that, in mice, the health effects of crowding may be explained at least in part by chemosignals and also propose a significant role of stress and genome destabilization in the emergence of crowding effects.

'Trojan-Horse' stress-granule formation mediated by manganese oxide nanoparticles.

Exposure to nanomaterials is considered as one of the risk factors for neurodegenerative pathology. In vitro inorganic nanoparticles (NPs) absorb intrinsically disordered proteins, many of which are the constituents of stress-granules (SGs). SGs normally form in response to cellular stress and, here, we addressed whether selected inorganic NPs could trigger SGs formation in cells. To this end, we have tested a series of inorganic NPs for their ability to induce SGs formation in human glioblastoma and fibroblast cell lines. Among tested NPs, only Mn3O4 NPs triggered SGs formation in cell-type-specific and metabolic-dependent manner. In human glioblastoma U87 MG cell line, Mn3O4 NPs entered cells within minutes and resided inside intracellular vesicles for at least 48 h. Mn3O4 NPs induced a strong reduction in oxidative phosphorylation rate, but not glycolysis. We showed that Mn3O4 NPs slowly dissolve producing a local net of Mn2+ cations, which are known to inhibit oxidative phosphorylation. Indeed, direct incubation of cells with equimolar amounts of Mn2+ cations triggered SGs formation and reduced cellular respiration rate. However, while SGs formed in response to Mn3O4 NPs persisted for hours, SGs formation by Mn2+ peaked and dropped within minutes. Finally, Mn3O4 NPs mediated SGs formation via the phosphorylation of eIF2α. Thus, we conclude that exposure of U87 MG cells to Mn3O4 NPs caused a 'Trojan-horse' prolonged SGs response.

Modification of Fecal Bacteria Counts and Blood Immune Cells in the Offspring of BALB/c and C57BL/6 Mice Obtained through Interstrain Mouse Embryo Transfer.

The reproducibility of results obtained with rodent models depends on the genetic purity of the strain and the stability of the environment. However, another potential factor is changes in the gut microbiota due to the transmission of mother's bacteria during embryo transfer. In this study, we demonstrate the transmission of the microbiota and immune cell blood phenotype to the offspring of 2 strains, C57BL/6JNskrc and BALB/cJNskrc, from surrogate dams of different genotypes. Interstrain embryo transfer resulted in a change in the number of Enterococcus spp. organisms, as shown by quantitative PCR analysis. The number of blood leukocytes was also affected, as estimated by flow cytometry. The number of blood leukocytes, including B cells and helper T cells, and the number of Enterococcus spp. organisms in male C57BL/6JNskrc offspring bornto BALB/cJNskrc surrogate dams became similar to those of male BALB/cJNskrc mice born to BALB/cJNskrc dams. Likewise, the same parameters of male BALB/cJNskrc mice born to C57BL/6JNskrc dams became similar to those of male C57BL/6JNskrc offspring. Researchers should be aware of the possible transmission of the dam's microbiota and immune cell phenotypes to the experimental strains when planning embryo transfer experiments, because these factors could affect the experimental outcomes or the reproducibility of experimental results.

From Allostatic Load to Allostatic State-An Endogenous Sympathetic Strategy to Deal With Chronic Anxiety and Stress?

The concepts of allostatic load and overload, i. e., a dramatic increase in the allostatic load that predisposes to disease, have been extensively described in the literature. Here, we show that rats engaging in active offensive response (AOR) behavioral strategies to chronic predator scent stress (PSS) display less anxiety behavior and lower plasma cortisol levels vs. rats engaging in passive defensive response (PDR) behavioral strategies to chronic PSS. In the same chronic PSS paradigm, AOR rats also have higher lactate and lower glutamate levels in amygdala but not in control-region hippocampus vs. PDR rats. The implications of these findings for regulation of allostatic and stress responses, and post-traumatic stress disorder (PTSD) are discussed.

Phenotypic variations in transferred progeny due to genotype of surrogate mother.

STUDY QUESTION: Does the genotype of the surrogate mother modulate the body composition and immunity of her offspring? SUMMARY ANSWER: C57BL/6J (B6) progenies carried by immunodeficient NOD SCID (NS) mothers had increased adaptive but decreased innate, immune responsiveness in comparison with the same genotype offspring carried by immunocompetent mothers, B6 and BALB/c (C); the B6 progenies carried by the same genotype mothers also showed higher body fat than the others. WHAT IS KNOWN ALREADY: Differences in the major histocompatibility complex (MHC) genes between mother and foetus is considered as an important factor in prenatal embryo development, whereas the impact of such dissimilarity on the phenotype of the mature progeny is unclear. STUDY DESIGN, SIZE, DURATION: Transplantation of two-cell mouse embryos into recipient females of the different MHC (H2) genotypes was used as an approach to simulate three variants of the immunogenic mother-foetus interaction: (i) bidirectional immunogenic dialogue between B6 (H2b haplotype) embryos and C (H2d haplotype) surrogate mother; (ii) one-way immunogenic interaction between B6 embryos and immunodeficient NS (H2g7 haplotype) surrogate mother and (iii) reduced immunogenetic dialogue between embryos and surrogate mother of the same H2b haplotype resulting in only a maternal response to HY antigens of male foetuses. Delivered by Caesarean section, pups were fostered by lactating B6 females and weighed after weaning (n = 171). Body mass and composition and innate and adaptive immunity were assessed in selected progeny groups at 9-11 weeks of age. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was performed on the specific pathogen-free mouse, inbred strains C57BL/6J, NOD SCID and BALB/c. Plasma progesterone in pregnant females was measured by enzyme-linked immunosorbent assay (ELISA). Body composition was determined by magnetic resonance spectroscopy using a low-field NMR spectrometer (EchoMRI, USA). To assess peritoneal macrophage responses (innate immunity) to anthrax, lactate dehydrogenase (LDH) and interleukin-1 (IL-1ß) were measured in a culture medium 24 h after the addition of both anthrax-lethal factor and anthrax-protective antigen. To assess adaptive immunity, 9-10 males in experimental groups were infected with Helicobacter hepaticus. Faeces collected 2 and 4 weeks after infection was used for quantitative assessment of the H. hepaticus DNA by real-time polymerase chain reaction. IgA, interferon (IFN-γ), tumour necrosis factor (TNFα), interleukin-17 (IL-17) and interleukin-10 (IL-10) in colon tissue and IgG in serum were determined in samples collected 4 weeks after gavage with H. hepaticus using ELISA. For statistical analyses, ANCOVA, post hoc least significant difference (LSD) test, Student's t-test, Spearman rank correlations and χ2 test were performed. P-value <0.05 was considered as a statistically significant difference. MAIN RESULTS AND THE ROLE OF CHANCE: ANCOVA with litter size and age as covariates revealed significant effects of the surrogate mother genotype on body mass and percent of fat in their adult progeny (F2149 = 15.60, P < 0.001 and F2149 = 5.02, P = 0.007, respectively). Adult B6 mice carried by B6 surrogate mothers were characterized by a higher percentage of body fat in comparison with offspring that were carried by NS and C females. In comparison with the male offspring carried by the B6 and C mothers, male B6 progenies carried by immunodeficient NS mothers had a higher humoral immune response (serum IgG) against oral infection with H. hepaticus, but lower in vitro macrophage IL-1ß reaction to the anthrax. Four weeks after the infection of offspring, concentrations of serum IgG and colon IL-10 correlated positively with maternal progesterone on Day 4 after embryo transfer and negatively with DNA of H. hepaticus. One-way ANOVA confirmed a statistically significant impact of surrogate mother genotype on adaptive (IgG) and innate (IL-1ß) immunity (F2.26 = 26.39, P < 0.001 and F2.27 = 5.89, P = 0.008, respectively). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The main limitation of our study is the number of combinations of mother and foetus interactions, in particular, transfer of only one embryo genotype was used. Also, it is a descriptive study, which requires further analysis of the epigenetic mechanisms of the observed phenotypic effects of surrogate mother genotype. WIDER IMPLICATIONS OF THE FINDINGS: Our experimental data demonstrate that the transfer of inbred embryos to surrogate mothers of the different genotypes is a prospective experimental model for the study of epigenetic effects of the immunogenetic interactions between mother and foetus. The experimental approach tested in our study will be in demand for the development of criteria for choosing surrogate mothers. In particular, immunocompetence of the surrogate mother along with genetic distance of her MHC alleles to the transferred embryos have a significant impact on offspring development. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Russian FPI (6/099/2017), budget projects (0324-2016-0002 and 0324-2018-0016) and implemented using the equipment of the Centre for Genetic Resources of Laboratory Animals at ICG SB RAS, supported by the Ministry of Education and Science of Russia (Unique project identifier RFMEFI62117X0015). The authors report no conflicts of interest.

GC-based chemoprofile of lipophilic compounds in Altaian Ganoderma lucidum sample.

The presented data contains information about component composition of lipophilic compounds in Ganoderma lucidum fungal body sample obtained using gas chromatography and subsequent mass spectrometry.

Hypotensive and neurometabolic effects of intragastric Reishi (Ganoderma lucidum) administration in hypertensive ISIAH rat strain.

BACKGROUND: As the standard clinically used hypotensive medicines have many undesirable side effects, there is a need for new therapeutic agents, especially ones of a natural origin. PURPOSE: One possible candidate is extract from the mushroom Reishi (Ganoderma lucidum), which is used in the treatment and prevention of many chronic diseases. STUDY DESIGN AND METHODS: To study the effectiveness of Reishi, which grows in the Altai Mountains, as an antihypertensive agent, we intragastrically administered Reishi water extract to adult male hypertensive ISIAH (inherited stress-induced arterial hypertension) rats. RESULTS: After seven weeks, Reishi therapy reduced blood pressure in experimental animals at a level comparable to that of losartan. Unlike losartan, intragastric Reishi introduction significantly increases cerebral blood flow and affects cerebral cortex metabolic patterns, shifting the balance of inhibitory and excitatory neurotransmitters toward excitation. CONCLUSION: Changes in cerebral blood flow and ratios of neurometabolites suggests Reishi has a potential nootropic effect.

Unexpected phenotypic effects of a transgene integration causing a knockout of the endogenous Contactin-5 gene in mice.

Contactins (Cntn1-6) are a family of neuronal membrane proteins expressed in the brain. They are required for establishing cell-to-cell contacts between neurons and for the growth and maturation of the axons. In humans, structural genomic variations in the Contactin genes are implicated in neurodevelopmental disorders. In addition, population genetic studies associate Contactins loci with obesity and hypertension. Cntn5 knockout mice were first described in 2003, but showed no gross physiological or behavioral abnormalities (just minor auditory defects). We report a novel Cntn5 knockout mouse line generated by a random transgene integration as an outcome of pronuclear microinjection. Investigation of the transgene integration site revealed that the 6Kbp transgene construct coding for the human granulocyte-macrophage colony-stimulating factor (hGMCSF) replaced 170 Kbp of the Cntn5 gene, including four exons. Reverse transcription PCR analysis of the Cntn5 transcripts in the wild-type and transgenic mouse lines showed that splicing of the transgene leads to a set of chimeric hGMCSF-Cntn5 transcript variants, none of which encode functional Cntn5 protein due to introduction of stop codons. Although Cntn5 knockout animals displayed no abnormalities in behavior, we noted that they were leaner, with less body mass and fat percentage than wild-type animals. Their cardiovascular parameters (heart rate, blood pressure and blood flow speed) were elevated compared to controls. These findings link Cntn5 deficiency to obesity and hypertension.

Multifunctional human serum albumin-therapeutic nucleotide conjugate with redox and pH-sensitive drug release mechanism for cancer theranostics.

We report on the synthesis and properties of a new multimodal theranostic conjugate based on an anticancer fluorinated nucleotide conjugated with a dual-labeled albumin. A fluorine-labeled homocysteine thiolactone has been used as functional handle to synthesize the fluorinated albumin and couple it with a chemotherapeutic agent 5-trifluoromethyl-2'-deoxyuridine 5'-monophosphate (pTFT). The conjugate allows for direct optical and 19F magnetic resonance cancer imaging and release of the drug upon addition of glutathione. Interestingly, the pTFT release from albumin conjugate could only be promoted by the increased acidity (pH 5.4). The in vitro study and primary in vivo investigations showed stronger antitumor activity than free pTFT.

Nanoparticles Associate with Intrinsically Disordered RNA-Binding Proteins.

Nanoparticles are capable of penetrating cells, but little is known about the way they interact with intracellular proteome. Here we show that inorganic nanoparticles associate with low-complexity, intrinsically disordered proteins from HeLa cytosolic protein extracts in nondenaturing in vitro nanoparticle pull-down assays. Intrinsic protein disorder associates with structural mobility, suggesting that side-chain flexibility plays an important role in the driving of a protein to nanoparticle absorption. Disordered protein domains are often found in a diverse group of RNA-binding proteins. Consequently, the nanoparticle-associated proteomes were enriched in subunits of RNA-processing protein complexes. In turn, this indicates that within a cell, nanoparticles might interfere with protein synthesis triggering a range of cellular responses.

Modulation of embryonic development due to mating with immunised males.

The modification of pre- and postnatal development conferred by immunogenic stimulation of mothers provides a population-level adaptation mechanism for non-genetic transfer of maternal experiences to progeny. However little is known about the transmission of paternal immune experiences to offspring. Here, we show that immune priming of males 3-9 days before mating affects the growth and humoral environment of developing embryos of outbred (ICR) and inbred (C57BL and BALB/c) mice. Antigenic stimulation of fathers caused a significant increase in embryonic bodyweight as measured on Day 16 of pregnancy and altered other gestation parameters, such as feto-placental ratio. Pregnant females mated with immunised males were also characterised by changes in humoral conditions as shown by measurements of blood and amniotic progesterone, testosterone and granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine concentrations. These results emphasise the role of paternal effects of immune priming on the in utero environment and fetal growth.

Eradication of Helicobacter spp. in mucin2-deficient mice.

Infections with Helicobacter spp. are known to have serious effects on rodent health, especially in immunocompromised animals. In this study three approaches were used to eradicate Helicobacter spp. infection in mice with a deficiency in intestinal proteoglycan (mucin2), namely triple oral antibiotic therapy (amoxicillin, clarithromycin and metronidazole), cross-fostering of neonatal pups by surrogate mothers negative for Helicobacter spp., and in vitro fertilization (IVF) with embryo transfer into Helicobacter-free mothers. However, triple antibiotic therapy in mice with mucin2 deficiency was not effective and had negative effects on reproductive performance, and high susceptibility of mucin2-deficient mice to Helicobacter spp. during the first 12 h after birth rendered cross-fostering impossible. Only IVF with embryo transfer was effective in eradicating Helicobacter infection from transgenic mice with mucin2 deficiency.

Knockout Zbtb33 gene results in an increased locomotion, exploration and pre-pulse inhibition in mice.

The Zbtb33 gene encodes the Kaiso protein-a bimodal transcriptional repressor. Here, the effects of Zbtb33 gene disruption on the brain and behaviour of the Kaiso-deficient (KO) and C57BL/6 (WT) male mice were investigated. Behaviour was studied using the open field, novel object, elevated plus maze and acoustic startle reflex tests. Brain morphology was investigated with magnetic resonance imaging. Biogenic amine levels and gene expression in the brain were measured with high-performance liquid chromatography and quantitative real-time RT-PCR, respectively. Zbtb33 gene mRNA was not detected in the brain of KO mice. KO mice exhibited increased locomotion, exploration in the open field, novel object and elevated plus-maze test. At the same time, Zbtb33 gene disruption did not alter anxiety-related behaviour in the elevated plus-maze test. KO mice showed elevated amplitudes and pre-pulse inhibitions of the acoustic startle reflex. These behavioural alterations were accompanied by significant reductions in the volumes of the lateral ventricles without significant alterations in the volumes of the hippocampus, striatum, thalamus and corpus callosum. Norepinephrine concentration was reduced in the hypothalami and hippocampi in KO mice, while the levels of serotonin, dopamine, their metabolites as well as mRNA of the gene coding brain-derived neurotrophic factor were not altered in the brain of KO mice compared to WT mice. This study is the first to reveal the involvement of the Zbtb33 gene in the regulation of behaviour and the central nervous system.

Comparative study of perception and processing of socially or sexually significant odor information in male rats with normal or accelerated senescence using fMRI.

Olfaction plays an important role in mammals while aging causes olfactory dysfunction. Here the features of olfactory function in aging male rats were studied. We compared brain activity of regions involved in the perception (olfactory bulbs) and processing (cerebral cortex, hippocampus, hypothalamus) of sexually or socially significant odor stimulus with 11.7 T MR-scanner and odor perception using behavioral tests in 5-month old males with normal (Wistar rats) or accelerated senescence (d-galactose-treated Wistar rats (150 mg/kg/day, i.p., 12 weeks) or OXYS rats with hereditary defined accelerated aging). d-galactose-treated Wistar males had altered BOLD-response in the centers processing socially significant odor information and changed patterns of the functional connectivity. We detected no significant changes in the olfactory function of OXYS males probably due to compensatory processes. In saline-treated Wistar rats, the correlation of BOLD-responses to both types of stimuli in the olfactory bulbs and cerebral cortex indicated changes in odor differentiation. Behavioral tests showed no significant differences between groups. However, the time of odor exploration increased in d-galactose-treated males indicating changes in odor recognition. Thus, we first revealed that in animal model of pharmacologically induced aging olfactory dysfunction occurred at the level of the centers processing socially significant odor information while the centers of odor perception (olfactory bulbs) remained unaffected. Alterations observed in Wistar rats chronically treated with saline evidenced the influence of long-term manipulations with experimental animals on olfactory function per se.

Neurometabolic Effect of Altaian Fungus Ganoderma lucidum (Reishi Mushroom) in Rats Under Moderate Alcohol Consumption.

BACKGROUND: The medications produced from natural products are widely used as prophylactics for sickness induced by alcohol consumption. One such prophylactic is produced from the Reishi mushroom, Ganoderma lucidum. Because of the antioxidant properties of these preparations, we expect neuroprotective prophylactic effects of Reishi-based medications in alcohol-treated animals. METHODS: The Reishi (R) suspension was produced as water extract from Altaian mushrooms. Sprague-Dawley male rats were separated into the following 3 experimental groups: Group A + R received R (6 days per week) starting 1 week before alcohol exposure, and during the next 3 weeks, they received both R and alcohol; group A received alcohol; and group C received water. At the end of experiment, we determined the metabolic profile using proton magnetic resonance spectroscopy ((1) H MRS) of the brain cortex and phosphorus magnetic resonance spectroscopy of the liver. Additionally, the blood cells were collected, and the serum biochemistry and liver histology were performed after euthanasia. RESULTS: Partial least squares discriminant analysis processing of the brain (1) H MRS gave 2 axes, the Y1 axis positively correlated with the level of taurine and negatively correlated with the level of lactate, and the Y2 axis positively correlated with the content of GABA and glycine and negatively correlated with the sum of the excitatory neurotransmitters, glutamate and glutamine. The Y1 values reflecting the brain energetics for the A + R group exceeded the corresponding values for groups C and A. The maximal level of Y2 reflecting the prevalence of inhibitory metabolites in the brain was observed in the rats exposed to alcohol. Moderate alcohol consumption did not cause significant pathological changes in the livers of the experimental animals. However, 20 days of alcohol consumption significantly increased the number of binuclear hepatocytes compared to the control. This effect was mitigated in the rats that received the Reishi extract. CONCLUSIONS: Regular administration of the Reishi suspension improved the energy supply to the brain cortex and decreased the prevalence of inhibitory neurotransmitters that are characteristic of alcohol consumption. The alcohol-induced increase in liver proliferation was significantly suppressed by regular administration of the G. lucidum water suspension.

Transgenic carrot expressing fusion protein comprising M. tuberculosis antigens induces immune response in mice.

Tuberculosis remains one of the major infectious diseases, which continues to pose a major global health problem. Transgenic plants may serve as bioreactors to produce heterologous proteins including antibodies, antigens, and hormones. In the present study, a genetic construct has been designed that comprises the Mycobacterium tuberculosis genes cfp10, esat6 and dIFN gene, which encode deltaferon, a recombinant analog of the human γ-interferon designed for expression in plant tissues. This construct was transferred to the carrot (Daucus carota L.) genome by Agrobacterium-mediated transformation. This study demonstrates that the fusion protein CFP10-ESAT6-dIFN is synthesized in the transgenic carrot storage roots. The protein is able to induce both humoral and cell-mediated immune responses in laboratory animals (mice) when administered either orally or by injection. It should be emphasized that M. tuberculosis antigens contained in the fusion protein have no cytotoxic effect on peripheral blood mononuclear cells.

Genetic basis of olfactory cognition: extremely high level of DNA sequence polymorphism in promoter regions of the human olfactory receptor genes revealed using the 1000 Genomes Project dataset.

The molecular mechanism of olfactory cognition is very complicated. Olfactory cognition is initiated by olfactory receptor proteins (odorant receptors), which are activated by olfactory stimuli (ligands). Olfactory receptors are the initial player in the signal transduction cascade producing a nerve impulse, which is transmitted to the brain. The sensitivity to a particular ligand depends on the expression level of multiple proteins involved in the process of olfactory cognition: olfactory receptor proteins, proteins that participate in signal transduction cascade, etc. The expression level of each gene is controlled by its regulatory regions, and especially, by the promoter [a region of DNA about 100-1000 base pairs long located upstream of the transcription start site (TSS)]. We analyzed single nucleotide polymorphisms using human whole-genome data from the 1000 Genomes Project and revealed an extremely high level of single nucleotide polymorphisms in promoter regions of olfactory receptor genes and HLA genes. We hypothesized that the high level of polymorphisms in olfactory receptor promoters was responsible for the diversity in regulatory mechanisms controlling the expression levels of olfactory receptor proteins. Such diversity of regulatory mechanisms may cause the great variability of olfactory cognition of numerous environmental olfactory stimuli perceived by human beings (air pollutants, human body odors, odors in culinary etc.). In turn, this variability may provide a wide range of emotional and behavioral reactions related to the vast variety of olfactory stimuli.

Proton magnetic resonance spectroscopy of brain metabolic shifts induced by acute administration of 2-deoxy-d-glucose and lipopolysaccharides.

In vivo proton magnetic resonance spectroscopy ((1) H MRS) of outbred stock ICR male mice (originating from the Institute of Cancer Research) was used to study the brain (hippocampus) metabolic response to the pro-inflammatory stimulus and to the acute deficiency of the available energy, which was confirmed by measuring the maximum oxygen consumption. Inhibition of glycolysis by means of an injection with 2-deoxy-d-glucose (2DG) reduced the levels of gamma-aminobutyric acid (GABA, p < 0.05, in comparison with control, least significant difference (LSD) test), N-acetylaspartate (NAA, p < 0.05, LSD test) and choline compounds, and at the same time increased the levels of glutamate and glutamine. An opposite effect was found after injection with bacterial lipopolysaccharide (LPS) - a very common pro-inflammatory inducer. An increase in the amounts of GABA, NAA and choline compounds in the brain occurred in mice treated with LPS. Different metabolic responses to the energy deficiency and the pro-inflammatory stimuli can explain the contradictory results of the brain (1) H MRS studies under neurodegenerative pathology, which is accompanied by both mitochondrial dysfunction and inflammation. The prevalence of the excitatory metabolites such as glutamate and glutamine in 2DG treated mice is in good agreement with excitation observed during temporary reduction of the available energy under acute hypoxia or starvation. In turn, LPS, as an inducer of the sickness behavior, which was manifested as depression, sleepiness, loss of appetite etc., shifts the brain metabolic pattern toward the prevalence of the inhibitory neurotransmitter GABA.

Hereditary catalepsy in mice is associated with the brain dysmorphology and altered stress response.

Catalepsy is a passive defensive strategy in response to threatening stimuli. In exaggerated forms it is associated with brain dysfunctions. The study was aimed to examine (1) possible association of the hereditary catalepsy with neuroanatomical characteristics and (2) sensitivity of the catalepsy expression, HPA and brain serotonin (5-HT) systems to restraint stress (for one hour) in mice of catalepsy-prone (CBA/Lac, ASC (Antidepressant Sensitive Catalepsy), congenic AKR.CBA-D13M76) and catalepsy-resistant (AKR/J) strains. Magnetic resonance imaging showed that the catalepsy-prone mice were characterized by the smaller size of the pituitary gland and the larger size of the thalamus. In ASC mice, diencephalon region (including hypothalamus) and striatum were significantly reduced in size. Restraint stress provoked catalepsy in AKR mice and enhanced it in the catalepsy-prone mice. Stress-induced corticosterone elevation was diminished, while 5-HT metabolism (5-HIAA level or 5-HIAA/5-HT ratio) in the midbrain was significantly augmented by stress in the catalepsy-prone mice. The multivariate factor analysis revealed interactions between the basal levels and the stress-induced alterations of 5-HT metabolism in the hippocampus and midbrain suggesting the interaction between multiple alterations in 5-HT neurotransmission in several brain structures in the regulation of hereditary catalepsy. The study indicated an association between the hereditary catalepsy, neuroanatomical characteristics, and neurochemical responses to emotional stress. The catalepsy-prone genotypes seem to be more susceptible to stress that suggests them as the adequate models to study the genetic predisposition to stress-based neuropathology. The data support the association of hereditary catalepsy with the inherited brain dysfunction of a neurodegenerative nature.

IL-1ß-independent activation of lung immunity in male mice by female odor.

In previous studies, we showed that long-term perception of female odor increases flu virus resistance in male mice. To expand on this finding, we examined the ability of female chemical cues to rapidly induce leukocyte mobilization into male lung tissue as a critical condition of signal-derived respiratory infection risk reduction, which is usually associated with sniffing scent marks. Here, we compared the immune and endocrine effects of female chemical cues and lipopolysaccharide (LPS) as common triggers of innate immunity. The number of leukocytes in the lung tissue, concentrations of IL-1ß in lung and hypothalamus, and plasma corticosterone and testosterone levels were assessed in ICR male mice 2h after the intranasal application of female urine, LPS or urine and LPS. Both stimuli induced leukocyte mobilization but, in contrast to LPS, female urine alone did not stimulate increased IL-1ß levels in lung and hypothalamus. Plasma corticosterone increased and plasma testosterone decreased in response to LPS, whereas the concentrations of these hormones did not change in response to female chemical cues. Thus, the present study gives additional evidence for an anticipatory adaptation of male mice to potential breeding risks. Appreciable mobilization of leukocytes to the lungs requires less than 2h and develops through an IL-1ß-independent pathway.