Male odors that influence the preference of female mice: roles of urinary and preputial factors

Female mice preferred to investigate the odor of normal male urine to that of either castrated or preputialectomized male urine. Females showed no particular preferences in two-choice tests among castrated, castrated-preputialectomized and preputialectomized male urine. These results suggest that both urinary and preputial factors of males are involved in female attraction. In an experiment with urine mixtures, females preferred a mixture of urine from preputialectomized males and castrated males to a mixture of urine from preputialectomized males and castrated-preputialectomized males. This strongly suggests that the urinary factor is androgen-dependent, while the preputial factor is possibly androgen-independent. Further experiments demonstrated the possibility that the preputial odorous factor involved in female attraction is increased or newly formed after excretion of the secretion.     

Effect of vomeronasal organ removal from male mice on their preference for and neural Fos responses to female urinary odors

Four experiments were conducted to determine whether vomeronasal organ (VNO) inputs in male mice mediate the rewarding properties of estrous female urinary odors. Sexually naive male mice with either an intact (VNOi) or lesioned (VNOx) VNO preferred to investigate female urine over water in Y-maze tests. Subsequently, VNOi males ran significantly more quickly and remained in nasal contact longer with estrous female urine than with male urine, whereas VNOx males investigated these odors equally. In home-cage habituation-dishabituation tests, VNOi males also investigated female urine significantly longer than did VNOx males, although both groups investigated female urine longer than other non-body odors. Finally, female urinary odors induced Fos in the nucleus accumbens core of VNOi males but not of VNOx males. Our results suggest that female urinary odors retain some incentive value in VNOx males. However, once direct nasal contact is made with female urine, VNO inputs further activate forebrain mechanisms that amplify the reward salience of this stimulus for the male mouse.     

Female hamster preference for odors is not regulated by circulating gonadal hormones

Proceptive and receptive behaviors of female rodents, such as golden hamsters, are often regulated by changes in circulating levels of ovarian hormones. However, less is known about how ovarian hormones might regulate female hamster's attraction and preference for volatile odor from males. To evaluate this, we assessed female preference by recording investigation and proximity to male and female volatile odorants in a Y-maze across all days of the estrous cycle (Experiments 1 and 2) or following ovariectomy (Experiment 3). In Experiment 1, female subjects were tested four times, once on each day of their estrous cycle. Females showed a preference for male odors on diestrus day 1 and to a lesser degree on proestrus, but showed no preference on the day of behavioral estrus. Irrespective of cycle day, preference was apparent in the first few days of testing and disappeared by the fourth day, suggesting that repeated testing attenuated female preference. To avoid this problem, in Experiment 2 each animal was tested only on one day of the 4-day estrous cycle. Female preference for male volatile odors over those from females was observed on each day of their estrous cycle, including estrus. Moreover, following gonadectomy (Experiment 3) female hamsters still preferred male volatile odors to those of females. Taken together, this suggests that circulating levels of gonadal hormones do not influence preference for male volatile odors in female hamsters.     

Organ distinctive mutagenicity in MutaTMMouse after short-term exposure to PhIP

We have investigated PhIP-induced mutagenicity in various tissues(Kidney, liver, large and small intestine) using a transgenicmouse model (Muta^TMMouse). In addition to tissue specific mutagenesis,we measured the binding of [¹⁴C]PhIP to Muta^TMMouse mice bloodproteins (haemoglobin and albumin), to obtain a quantitativeestimate of carcinogen exposure and activation and their relationshipto mutagenesis. Short-term (4 days) treatment of Muta^TMMousemice with [¹⁴C]PhIP by oral gavage resulted in the dose-dependentaccumulation of radiolabelled material bound to haemoglobinand serum albumin. PhIP, at the highest dose (20 mg/kg), causeda 5.9-fold increase in the mutation frequency in the large intestine,a 4.2-fold increase in the mutation frequency in the small intestinebut only a marginal 1.6-fold increase in the liver. However,there was no significant increase in mutations in the kidneyat this dose. In contrast, there were no significant differencesin any of these tissues between the vehicle control and thetwo lower doses (2.0 and 0.2 mg/kg respectively). These resultsare discussed in relationship to those previously reported forPhIP at the Dlb-1 locus. ¹To whom correspondence should be addressed     

Development of sex differences in the response of spiny mouse pups to adult male odors

Using a three-choice preference test, olfactory-mediated investigatory activity in response to adult male urine odor was examined in a precocially active rodent, the spiny mouse (Acomys cahirinus) aged between 3-26 days. Temporally related sex differences were seen in the time spent in the presence of the odors of father's or unfamiliar adult male's urine, or distilled (control) water. Neither male nor female pups discriminated between odors from the father and strange adult males. After the first olfactory test, when the pups were aged between four and six days, male pups strongly preferred to stay in the vicinity of urine odors of adult males, whereas female pups avoided odors of adult males and remained in the enclosure with the control odor source. To our knowledge this is the first time that such a behavioral sex difference related to olfaction has been shown to occur in young rodent pups. We suggest that the sexually dimorphic response of the pups is associated with the development of later sex differences in behavior.     

亚硝酸盐暴露致雄性小鼠生殖毒性的探讨

目的 探讨亚硝酸盐暴露对雄性小鼠生殖毒性的分子机制。 方法 36只2月龄健康雄性小鼠,随机分为对照组(生理盐水）、低剂量组（60 mg/kg）和高剂量组（120 mg/kg）,每组12只进行亚硝酸盐灌胃3个月,观察小鼠的生长状况,HE染色法观察睾丸组织病理变化,免疫荧光和Western blotting方法分析检测睾丸组织细胞增殖与凋亡情况及DNA甲基化、组蛋白去乙酰化相关酶的表达情况。 结果 亚硝酸盐暴露组小鼠较对照组小鼠体重增加缓慢,睾丸指数降低（P<0.01）,形态发生病理性改变;亚硝酸盐暴露组小鼠睾丸组织细胞增殖较对照组明显减少,细胞凋亡较对照组明显增加（P<0.01）;同时DNA甲基化和组蛋白去乙酰化水平高于对照组（P<0.01）,且均具有剂量依赖性。 结论 亚硝酸盐暴露通过抑制雄性小鼠生长发育及睾丸生精细胞增殖,诱导睾丸生精细胞凋亡,造成雄性生殖毒性;DNA甲基化及组蛋白去乙酰化水平升高,提示表观遗传学可能参与了亚硝酸盐暴露对雄性生殖系统的损伤过程及调控机制。     

Source and item memory for odors and objects in children and young adults

Recall and recognition memory for odors are poorer in children than in adolescents. In addition, children perform worse than young adults on source memory tasks using visual and auditory stimuli. However, source memory for odor stimuli has not been examined in children. This study investigated source and item memory for odors and objects in children (7-10 years old) and young adults (18-24 years old). During the study phase, 1 male and 1 female experimenter (sources) randomly presented either 16 odors or 16 objects to the participant. Presentation alternated between sources so that each source presented 8 stimuli. Once the 16 stimuli were presented, the sources exited and a third experimenter began the test phase. To assess item recognition memory, a stimulus from the study phase and a novel stimulus were presented to the participant who was asked to choose the stimulus presented during the study phase. Source memory was assessed with the 8 stimuli from the study phase not used in the item memory task. The experimenter presented a stimulus and asked whether the male or female experimenter had presented the stimulus during the study phase. Results indicate that difference scores between item and source memory for odors were significantly larger for children than for young adults, indicating poorer source memory for children than adults. Difference scores for objects did not distinguish between groups. It has been suggested that the frontal lobes play a critical role in source memory and odor memory—a brain region that continues to develop into adolescence. Poor performance among children on the source memory task for odors may be due in part to immaturity of the frontal lobes.     

长期甲醛暴露对幼年小鼠学习记忆能力的影响

目的:研究长期甲醛暴露对幼年小鼠学习记忆能力的影响及分子机制。方法:将72只幼年C57BL/6小鼠分为对照组(control)、低浓度甲醛暴露组(FA-L)、中浓度甲醛暴露组(FA-M)和高浓度甲醛暴露组(FAH)。小鼠进行为期30 d不同浓度的甲醛暴露,称量小鼠体重变化,然后通过Morris水迷宫实验检测各组小鼠学习记忆能力,利用Nissl染色观察小鼠海马神经元结构变化,利用商品化试剂盒检测海马组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,利用Western Blot检测active caspase-3和Bcl-2等分子的表达变化。结果:与对照组小鼠相比,甲醛暴露小鼠体重增长缓慢,学习记忆能力下降,海马神经元数量减少,海马组织中SOD活性下降,MDA生成增加,active caspase-3水平增加,同时Bcl-2表达下降。结论:长期甲醛暴露可导致小鼠学习记忆能力下降,其作用机制与氧化应激反应增加并导致海马细胞凋亡有关。     

Two strategies for coping with food shortage in desert golden spiny mice

Desert rodents face periods of food shortage and use different strategies for coping with it, including changes in activity level. Golden spiny mice (Acomys russatus) inhabit rock crevasses and do not dig burrows nor store food. When kept under 50% food restriction most, but not all, golden spiny mice defend their body mass by physiological means. We tested the hypothesis that these rodents use two different behavioral strategies, i.e., increasing activity level and searching for food or decreasing activity level and conserving energy to cope with food shortage. Twelve golden spiny mice were fed ad libitum for 14 days, followed by 40 days of 50% food restriction, and 14 days of refeeding. Body mass, food consumption and general activity were monitored. Seven mice significantly reduced activity level, concentrating their activity around feeding time, lowering energy expenditure and thus keeping their body mass constant ("resistant"), while five ("non-resistant") significantly increased activity level (possibly searching for food) and thus energy expenditure, thereby losing mass rapidly (more than 25% of body mass). The non-resistant golden spiny mice were active throughout many hours of the day, with high variability both between and among individuals. The use of two strategies to cope with food shortage as found in the golden spiny mice may be of evolutionary advantage, since it allows a more flexible reaction to food restriction at the population level.     

Early exposure to odors changes later visual prey preferences in cuttlefish

Developmental studies have shown that environmental stimulation received by a developing sensory system can alter the developmental outcome of both that sensory system and other aspects of the nervous system. We investigated the ecologically relevant question of whether prior exposure to prey early in development within one sensory modality could influence later prey choice within a different sensory modality. Cuttlefish are visual predators; they can detect prey odors but attacks on prey cannot be elicited without visual stimulation. Cuttlefish eggs were exposed to the odor of shrimp (preferred prey), crabs (non-preferred prey), mollusks (non-prey), or a seawater control (no prey). Seven days after hatching, prey preferences were tested with a visual choice test between crabs and shrimp. Hatchlings exposed to crabs odors and the seawater control were significantly more likely to attack shrimp. Hatchlings exposed to mollusk odors showed no visual prey preference, while those exposed to shrimp preferentially attacked crabs. These results demonstrate a complex relationship between an early sensory exposure and later prey preference     

Late-in-life neurodegeneration after chronic sleep loss in young adult mice

Chronic short sleep (CSS) is prevalent in modern societies and has been proposed as a risk factor for Alzheimer’s disease (AD). In support, short-term sleep loss acutely increases levels of amyloid β (Aβ) and tau in wild type (WT) mice and humans, and sleep disturbances predict cognitive decline in older adults. We have shown that CSS induces injury to and loss of locus coeruleus neurons (LCn), neurons with heightened susceptibility in AD. Yet whether CSS during young adulthood drives lasting Aβ and/or tau changes and/or neural injury later in life in the absence of genetic risk for AD has not been established. Here, we examined the impact of CSS exposure in young adult WT mice on late-in-life Aβ and tau changes and neural responses in two AD-vulnerable neuronal groups, LCn and hippocampal CA1 neurons. Twelve months following CSS exposure, CSS-exposed mice evidenced reductions in CA1 neuron counts and volume, spatial memory deficits, CA1 glial activation, and loss of LCn. Aβ ₄₂ and hyperphosphorylated tau were increased in the CA1; however, amyloid plaques and tau tangles were not observed. Collectively the findings demonstrate that CSS exposure in the young adult mouse imparts late-in-life neurodegeneration and persistent derangements in amyloid and tau homeostasis. These findings occur in the absence of a genetic predisposition to neurodegeneration and demonstrate for the first time that CSS can induce lasting, significant neural injury consistent with some, but not all, features of late-onset AD.     

Endocannabinoid-mediated short-term suppression of excitatory synaptic transmission to medium spiny neurons in the striatum

Medium spiny neurons in the dorsal striatum receive glutamatergic excitatory synaptic inputs from the cerebral cortex. These synapses undergo long-term depression that requires release of endocannabinoids from medium spiny neurons and activation of cannabinoid CB1 receptors. However, it remains unclear how cortico-striatal synapses exhibit endocannabinoid-mediated short-term suppression, which has been found in various brain regions including the hippocampus and cerebellum. Endocannabinoids are released from postsynaptic neurons by strong depolarization and resultant Ca2+ elevation or activation of postsynaptic Gq/11-coupled receptors such as group I metabotropic glutamate receptors (mGluRs) and M1/M3 muscarinic acetylcholine receptors. Moreover, endocannabioids are effectively released when weak depolarization is combined with Gq/11-coupled receptor activation. We found that muscarinic activation induced transient suppression of excitatory synaptic transmission to medium spiny neurons, which was independent of retrograde endocannabinoid signaling but was mediated directly by presynaptic muscarinic receptors. Neither postsynaptic depolarization alone nor depolarization and muscarinic activation caused suppression of cortico-striatal synapses. In contrast, activation of group I mGluRs readily suppressed cortico-striatal excitatory synaptic transmission. Furthermore, postsynaptic depolarization induced clear suppression when combined with group I mGluR activation. These results indicate that group I mGluRs but not muscarinic receptors contribute to endocannabinoid-mediated short-term suppression of cortico-striatal excitatory synaptic transmission.     

The preputial glands as a source of aggression-promoting odors in mice

Injection of testosterone propionate (TP) into female mice increases aggressive attacks from males, and the size of their preputial glands. Experiments were designed to relate these two findings. Spayed females injected with TP increased the aggressiveness of previously mated, isolated males. This aggressiveness was reduced by preputialectomy of such females, though not to the level of that elicited by placebo-injected controls. The urine of spayed, TP-injected females was shown to contain an aggression-eliciting pheromone, which induced male fighter mice to increase their aggressiveness towards castrate male opponents. The effectiveness of this pheromone was not reduced by preputialectomy. It is concluded that androgens can stimulate the release of aggression-eliciting pheromone from two sources in the female. One, from the preputial glands, it is suggested, might act as a social signaling device during agonistic encounters and the other, present in the urine, might control wider aspects of behavior in mouse populations.     

Interferon-alpha prevents apoptosis of endothelial cells after short-term exposure but induces replicative senescence after continuous stimulation

Although the antiangiogenic activity of type I interferons (IFN) is well known, the mechanism by which it occurs is unclear. In the present study, we have investigated effects of short-term and long-term IFN-alpha exposure on different types of endothelial cells (EC). Short-term IFN-alpha treatment resulted in a distinct reduction of apoptosis of serum and growth factor starved HUVEC and HDMEC. This was accompanied by a strong upregulation of the IFN inducible guanylate binding protein-1 (GBP-1) whereas no consistent regulation of several known antiapoptotic proteins was evident. Stable transfection of HUVEC with an expression vector for GBP-1 mimicked the protective effect of IFN-alpha, suggesting that GBP-1 may contribute to the inhibition of apoptosis. When IFN-alpha, together with serum and EC growth factors, was present continuously a decrease of population doublings by more than 40% was observed in both HDMEC and HCAEC. In addition, the cells displayed a senescent phenotype significantly earlier than control cells and showed an increased adherence for monocytes. Our findings suggest that the antiangiogenic effect of IFN-alpha is mediated by inducing EC senescence rather than EC apoptosis. Furthermore IFN-alpha released in chronic inflammatory conditions might contribute via its prosenescent activity to the pathogenesis of atherosclerosis.     

Suppression of IgE antibody production after exposure to ozone in mice

The effect of ozone exposure on IgE antibody production with aerosolized ovalbumin (OA) administration was investigated in Balb/c mice. Mice were continuously exposed to 0.8 ppm ozone for 1, 2, or 4 weeks, respectively, and subsequently aerosolized OA was administered through the respiratory tract for 6 min with a nebulizer. The mice were then immunized intraperitoneally 1 week later with OA. IgE antibody production was suppressed in ozone-exposed mice. However, no significant difference in the primary IgE antibody production by intraperitoneal immunization alone with OA was observed between ozone-exposed mice and nonexposed mice. In order to elucidate the suppressive mechanism of IgE antibody production, hapten-carrier antigenic system was used. It is shown that the induction of helper T cell function was suppressed if the aerosolized carrier protein was administered before intraperitoneal immunization in the mice exposed to ozone. These results suggest that ozone exposure has the effect on the stage of administration of inhaled antigen and the quite insignificant effect on the IgE antibody production after intraperitoneal immunization with OA.     

Dimebon对小鼠中型多棘神经元NMDA激活电流的影响

目的：探讨药物Dimebon在阿尔茨海默氏病（AD）和亨廷顿氏病（HD）的药理作用。方法采用膜片钳技术在培养的小鼠纹状体中型多棘神经元（medium spiny striatal neurons,MSN）上观察不同浓度的Dimebon对NMDA (N-methyl-D-aspartic acid)受体激活电流的影响。结果高浓度的Dimebon抑制NMDA激活电流,而低浓度的Dimebon增强NMDA激活电流,从而下调NMDA受体。结论 Dimebon对NMDA受体激活电流的影响有双重作用,依Dimebon浓度的不同而不同,为临床用药提供依据。