M. P. Moshkin

Behaviour, chemosignals and endocrine functions in male mice infected with tick-borne encephalitis virus

Odour attractiveness, social behaviour and endocrine status of male mice (outbred ICR strain) were examined 6-7 days after inoculation with subclinical dose of tick-borne encephalitis virus (TBE). According to RT-PCR control of efficiency of infection, males injected with TBE were divided on the two subgroups: TBE+ (males with viral RNA) and TBE- (males without viral RNA). Susceptible males (TBE+ subgroup) showed the higher level of plasma testosterone in comparison with both control and nonsusceptible (TBE- subgroup) males. TBE+ males had also more odour attraction for oestrus females and more aggressiveness in social conflict. Higher sexual attractiveness and aggressiveness of the infected host benefit the pathogens distribution in the host population.

High level of circulating testosterone abolishes decline in scent attractiveness in antigen-treated male mice

We hypothesized that a decrease in the attractiveness of odours from infected male mice, Mus musculus could be caused by either parasite-induced changes in host metabolism (parasite-dependent pathway) or activation of the immune defence system (immune-dependent pathway). Activation of the immune defence system by nonreplicated antigens (sheep red blood cells, SRBC) is sufficient for a decrease in both scent attractiveness and the concentration of plasma testosterone in male mice. Since the scent attractiveness of male mice depends on androgen levels, we studied the olfactory effect of SRBC in sham-operated, gonadectomized and testosterone-treated male mice of the outbred strain ICR. SRBC administration resulted in a decline in both sexual odour attractiveness and concentration of urinary proteins in sham-operated control males. The effect of SRBC on concentration of urinary proteins was abolished by stabilizing the testosterone level in gonadectomized and androgen-treated males. At the same time, only the high dose of testosterone was sufficient to maintain the scent attractiveness in SRBC-treated males at the pretreatment level.

Epidemiology of a tick‐borne viral infection: theoretical insights and practical implications for public health

The morbidity of tick‐borne encephalitis (TBE) varies yearly by as much as 10‐fold among the people of Western Siberia. This long‐term variation is dependent on many factors such as the density of the tick populations, the prevalence of TBE virus (TBEV) among sub‐adult ticks, the yearly virulence of the TBEV, and prophylactic measures. Here we highlight the role of small mammal hosts in the circulation of TBEV through the ecosystem. Refining classical models of non‐viremic horizontal transmission, we emphasize the recently understood fact that the physiological and immunological status of the small mammal hosts affects the tick and virus‐host interactions. In addition to its theoretical interest, our approach may lead to some practical improvements in the precision of epidemiological forecasts and perhaps in forestalling the severity of outbreaks of TBE, or, at least, in forewarning medical authorities and the general public of impending TBE outbreaks.

PREDATION ON A SOCIAL DESERT RODENT, RHOMBOMYS OPIMUS: EFFECT OF GROUP SIZE, COMPOSITION, AND LOCATION

Abstract Predation can provide both positive and negative effects on formation of social groups in rodents. On the basis of observational data of predation by the desert monitor lizard (Varanus griseus caspius) on the great gerbil (Rhombomys opimus), a social rodent of desert Central Asia, we predicted that in a year after a peak in prey density, when the abundance of terrestrial predators is still high, the group mode of life of a prey species might become disadvantageous. Social groups could advertise themselves and attract predators. We therefore hypothesized that the probability of predation would be higher for gerbils in outlying social groups than in groups closely associated with each other, in larger compared with smaller groups, and in groups with an active adult male compared with solitary females with no resident male. We also analyzed whether the survival of gerbils and the stress levels in adult and juvenile males were related to frequency of visits by monitor lizards at gerbil colonies (isolated systems of burrows used by gerbil groups of any size), distance between colonies, and size of social groups. We found that frequency of visits by the monitor lizard depended on distance to the nearest neighboring colony. The more distant the gerbil colony, the more visits by the lizard and the lower the survival of juveniles. We also found a positive correlation between concentration of fecal corticosterone in young males and frequency of monitor lizard visits at colonies. This pattern was not as pronounced in adult males. Results did not support the hypothesis that larger groups would have higher predation because frequency of predator visits, distances to the nearest occupied colonies, and survival of juveniles did not correlate significantly with the size of family groups. There was no difference in survival of juveniles in colonies occupied by single females compared with colonies in which an adult male was present. These results suggest that there is a possible trade-off between competing strategies of antipredator behavior and that factors other than predation are influencing gerbil survival.

Female scent signals enhance the resistance of male mice to influenza.

Background The scent from receptive female mice functions as a signal, which stimulates male mice to search for potential mating partners. This searching behavior is coupled with infection risk due to sniffing both scent marks as well as nasal and anogenital areas of females, which harbor bacteria and viruses. Consideration of host evolution under unavoidable parasitic pressures, including helminthes, bacteria, viruses, etc., predicts adaptations that help protect hosts against the parasites associated with mating. Methods and Findings We propose that the perception of female signals by BALB/c male mice leads to adaptive redistribution of the immune defense directed to protection against respiratory infection risks. Our results demonstrate migration of macrophages and neutrophils to the upper airways upon exposure to female odor stimuli, which results in an increased resistance of the males to experimental influenza virus infection. This moderate leukocyte intervention had no negative effect on the aerobic performance in male mice. Conclusions Our data provide the first demonstration of the adaptive immunological response to female odor stimuli through induction of nonspecific immune responses in the upper respiratory tract.

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.

ADRENOCORTICAL AND BIOENERGETIC RESPONSES TO COLD IN FIVE SPECIES OF MURINE RODENT

Abstract Oxygen consumption, rectal temperature, and plasma concentrations of glucocorticoids, free fatty acids, and glucose were studied in 5 species of rodents after cold exposure that exceeded their homeostatic capability (7°C for 15 min). Adrenocortical responses and metabolic responses (oxygen consumption) to cold were large in 3 solitary, terrestrial species, dwarf hamsters (Phodopus sungorus, P. campbelli, and P. roborovskii) and were minimal in a colonial fossorial species, mole voles (Ellobius talpinus). Bank voles (Clethrionomys glareolus) showed intermediate responses. There were no interspecific differences in mobilization of main bioenergetic substrates (glucose and free fatty acids). Results are interpreted in terms of evolutionary changes of stress: reactivity was positively correlated with the rate of social stimuli and negatively correlated with physically stressful stimuli in the natural environment of the species.

[Sexual transmission of tick-borne encephalitis virus in laboratory mice].

Mating of males infected with tick-borne encephalitis virus (strain Sofyin) with intact females results in a marked decrease in the weight of embryos and an almost threefodl increase in embryonal mortality. Viral RNA was identified by the polymerase chain reaction in embryonal tissues of 2 out of 11 litters. In one case the infection of the progeny was confirmed by biological test.

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 (1H 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 1H 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. Copyright

Long‐Term Dynamics of Fecal Corticosterone in Male Great Gerbils (Rhombomys opimus Licht.): Effects of Environment and Social Demography

We examined the relationship among seasonal characteristics of climate, food, and population demography (social structure) and fecal corticosterone (CORT) concentrations over 6 yr in adult males of an arid‐adapted species, the great gerbil (Rhombomys opimus Licht., Gerbillidae, Rodentia), as a measure of chronic stress in high, low, and recovering population densities. Results showed yearly differences in the seasonal means of CORT, with the highest concentrations in the year of the highest population density. Analysis of year‐specific relationships revealed a positive correlation between mean CORT and total precipitation in January and February and a negative correlation with precipitation in March. In the beginning of spring, when gerbils were in maximum reproductive effort, CORT correlated positively with the saturation of burrow systems and with the number of adult females with an adult male. A linear stepwise regression of CORT in individual males in spring seasons of all 6 yr combined after removal of year effects revealed that CORT depended positively on the number of females associated with a single male but negatively on the abundance of annual herbs. Disappearance of adult males was not related to CORT in most cases. We found no correlation between overall mortality from season to season and mean CORT in either spring (March–May) or fall. In fact, we found a highly negative correlation between mean CORT and the proportion of disappeared males at the beginning of spring. Only at the high population density when cases of probable catastrophic mortality of all adults in the group were excluded was CORT of individual males related positively to their disappearance during the summer drought. Our results suggest that desert rodents with irregular population fluctuations are more sensitive to suppression by external factors than by density‐dependent mortality mediated by stress. The favorable feeding and climatic conditions may have compensated for density‐dependent increases of CORT and the negative effects it might have had on survival.