Phosphatidyl choline and avoidance performance in 17 month-old SEC/1ReJ mice

Male SEC/1ReJ mice aged 6 or 17 months were fed diets containing 0, 2, 4 and 8% added phosphatidyl choline. After 4 days on the test diets they were given 5 daily sessions of 100 trials each in the shuttle-box. The younger mice rapidly acquired an avoidance response and reached high, stable levels of performance. The older mice learned more slowly and reached significantly lower performance levels (p < 0.01). Phosphatidyl choline had no effect on performance of young mice, while in the older mice the highest dose level of phosphatidyl choline increased avoidance performance by nearly 30% (p < 0.05).     

Gangliosides activate Trk receptors by inducing the release of neurotrophins

Pro-inflammatory cytokines, especially Interleukin (IL)-6, are elevated in the brains and serum of very premature infants in association with perinatal infectious and hypoxic/ischemic insults. To determine potential adverse effects of IL-6 on brain development, cross-fostered litters of male cd-1 mice were injected subcranially with hyper-IL-6 or vehicle at postnatal day (pnd) 4 and examined for alterations in functional landmarks of CNS development. No acute injury response was evident at 1–7 days following hyper-IL-6 injection as determined by glial morphology and RNase protection assays for acute response genes, ICAM-1, iNOS, Mac-1, A-20, and EB-22. In preweanling mice, reflex ontogeny and physical markers of development were not altered; however, exposed mice demonstrated increased over-generalized motor responses (Fox Battery) leading to an overall impression of hyper-reactivity and hyperactivity. At pnd 24 and 80, assessment of autonomic, sensory, and motor systems (Functional Observation Battery) showed persistence of hyper-reactivity and hyperactivity. Learning and memory were assessed by passive avoidance (PA) at pnd 24 and by radial arm maze (RAM) in adults. Hyper-IL-6 exposure significantly impaired PA performance. RAM performance was similar between hyper-IL-6 and control groups in acquisition of win-shift task but hyper-IL-6 animals showed deficits on repeated acquisition task. The persistent hyperactive, hyper-reactive behavioral phenotype evident in hyper-IL-6 exposed mice appeared to interfere with performance on both learning and memory tasks, suggesting that early exposure of the developing brain to IL-6 can have persistent adverse functional effects and raising additional concerns for effects of immune mediators in premature infants.     

Genetic susceptibility to chlamydial salpingitis and subsequent infertility in mice.

Groups of mice from genetically defined inbred strains were infected genitally with a pathogenic human strain of Chlamydia trachomatis and their subsequent fertility was compared. The CBA, C3H (H-2o) and C3H/He-mg (H-2k) mice were less fertile than control mice, at least up to 6 months after infection. In contrast, fertility was not impaired in BALB/c mice or in congenic BALB/K mice, which had the H-2k haplotype. Reduced fertility was paralleled by the extent of histological oviductal inflammation in mice of each strain. No salpingitis was seen 21 days after infection in the BALB strains, but lesions were apparent in CBA and C3H strains up to about 70 days after inoculation and these sometimes developed into hydrosalpinges. These results indicate that susceptibility to chlamydial salpingitis and subsequent infertility is under genetic control. This control was not simply associated with the major H-2 gene complex, as mouse strains of the same haplotype (H-2k) differed in susceptibility. The fertility of BALB/c (H-2d) and BALB/K (H-2k) strains was no different from that of controls, and congenic C3H mice of differing H-2 haplotypes (H-2k and H-2o) showed reduced fertility. Although all the infected F1 (BALB/K x C3H/He-mg) mice produced litters at the same rate as untreated controls, the litters were considerably smaller. This was due to the occurrence of unilateral pregnancies in the mice inoculated under the ovarian bursae and possibly also to early fetal death in mice inoculated directly in the uterus. These findings emphasize the importance of early diagnosis and treatment of infection of the lower genital tract of women.     

Whole-body X-irradiation of mice accelerates polyploidization of hepatocytes

Male C57BL/6 mice were whole-body irradiated with 4.75 Gy of X-rays at the age of 2 months and killed at 2, 6, 12 and 19 months after irradiation. The percentage survival began to decline earlier and faster in the irradiated group than the controls up to 19 months after exposure when the study was terminated. The nuclear DNA content of individual hepatocytes was measured by a Feulgen-DNA microfluorometric method, and hepatocytes were classified into various ploidy classes. In the irradiated mice, the degree of polyploidization was significantly higher than the controls by 2 months after exposure and steadily increased up to 6 months after exposure. Thereafter, however, a slow return to the control level was found up to 19 months after irradiation. These results appear to support a hypothesis that radiation accelerates the ageing process as judged from hepatocyte polyploidization.     

Total body 4.5 Gy gamma irradiation-induced early delayed learning and memory dysfunction in the rat.

In an attempt to determine the consequences of total body radiation damage on learning and memory in the rat, twenty-eight male Wistar rats aged 4 months received 4.5 Gy total body gamma-irradiation (TBI) while 28 rats received sham irradiation. Sequential behavioral studies of negative reinforcement including a/ one- and b/ two-way avoidance tasks were undertaken. a/ One-way avoidance test: this test was performed before and after TBI. Prior to irradiation both groups were similar. At 20 days (D) and at 3 months post-TBI, irradiated rats had a significantly lower percentage of avoidance than controls but no statistical difference was found at 5 months post-TBI. b/ Two-way avoidance test: this test was performed only after TBI. At days 21, 22, 23, 24, (leaming) and at 4 or 6 months (recalls) post-TBI the mean percentage of avoidance was significantly lower in irradiated than in control rats. This study demonstrates that total-body exposure to 4.5 Gy gamma-irradiation induces behavioral dysfunction affecting learning and transitorily memory. These results suggest that a relatively low dose of total body irradiation can induce neurological complications, which persist 4-6 months later.     

Comparison of mammary tumorigenesis between litters in relation to mammary tumor virus antigenic expression in the milk of C3H/He mice

As a possible step to estimate the relationship between mammary tumor virus (MTV) and mammary tumorigenesis in mice, MTV antigenic expression in mother's milk and spontaneous mammary tumorigenesis in their daughters were compared between the 1st, the 2nd and the 3rd litters of the highly inbred strains of C3H/He mice with low mammary tumor incidence. While MTV antigenic expression was detected in all undiluted samples at each litter by immunodiffusion test, the amount of antigen as measured by the single radial immunodiffusion method was increased with increasing litter numbers. On the other hand, the development of preneoplastic mammary hyperplastic alveolar nodules was different little between litters and mammary tumor incidence by 13 months of age was very low with no difference in all litters. The pattern of estrous cycles and plasma prolactin level were also similar in each litter. The results suggest that spontaneous mammary tumorigenesis in mice is not always affected quantitatively by the amount of MTV when endocrine and genetical conditions are similar.     

Effects of leptin on memory processing

Leptin is a peptide hormone secreted by adipose tissue. Studies have shown that leptin crosses the blood-brain barrier (BBB) by a saturable transport system where it acts within the hypothalamus to regulate food intake and energy expenditure. Leptin also acts in the hippocampus where it facilitates the induction of long-term potentiation and enhances NMDA receptor-mediated transmission. This suggests that leptin plays a role in learning and memory. Obese mice and rats, which have leptin receptor deficiency, have impaired spatial learning. In disease states such as diabetes, humans and animals develop leptin resistance at the BBB. This suggests that low leptin levels in the brain may be involved in cognitive deficits associated with diabetes. In the current study, the effects of leptin on post-training memory processing in CD-1 mice were examined. Mice were trained in T-maze footshock avoidance and step down inhibitory avoidance. Immediately after training, mice received bilateral injections of leptin into the hippocampus. Retention was tested 1 week later in the T-maze and 1 day later in step down inhibitory avoidance. Leptin administration improved retention of T-maze footshock avoidance and step down inhibitory avoidance. Leptin administered 24 h after T-maze training did not improve retention when tested 1 week after training. SAMP8 mice at 12 months of age have elevated amyloid-beta protein and impaired learning and memory. We examined the effect of leptin on memory processing in the hippocampus of 4 and 12 months old SAMP8 mice. Leptin improved retention in both 4 and 12 months old SAMP8 mice; 12 month SAMP8 mice required a lower dose to improve memory compared to 4 months SAMP8 mice. The current results indicate that leptin in the hippocampus is involved in memory processing and suggests that low levels of leptin may be involved in cognitive deficits seen in disease states where leptin transport into the CNS is compromised.     

Presenilin-1/Presenilin-2双基因敲除小鼠脑中单胺类神经递质变化的研究

条件性presenilins双基因敲除小鼠(dKO小鼠)表现出类似阿尔茨海默症(AD)的大部分神经退行性病症,如Tau 蛋白磷酸化、神经元凋亡、皮层萎缩以及认知能力受损等．为探讨presenilins功能缺失、神经退行性症状与单胺类递质变化的相关性,利用毛细管电泳法检测6、9和12月龄dKO小鼠皮层、海马及其他前脑部位中各单胺类神经递质的含量．结果显示,与对照组相比,dKO小鼠皮层中单胺类神经递质在6月龄时显著降低,而随着年龄的增长,神经退行性病变加剧,递质浓度也均明显上升,在海马区,dKO小鼠单胺类递质则呈上升趋势,但仅6月龄时5-羟色胺和肾上腺素及12月龄时各递质的上升有统计学意义,前脑其他部位5-羟色胺和多巴胺递质在6、9月龄时与对照组相近,在12月龄时则显著降低,而去甲肾上腺素和肾上腺素在6月和12月龄时均呈降低趋势,且均有统计学差异(6月龄肾上腺素除外)．实验表明,单胺类神经递质在presenilins双基因敲除的小鼠前脑各区域中的水平均发生了随龄化的变化,且在前脑皮层、海马与前脑其他区域的变化趋势各有不同,而单胺类递质的变化是presenilins双基因敲除导致的直接结果还是间接结果,单胺类递质在AD样神经退性行病变中的作用如何,还有待于进一步的研究．     

Infertility in mice infected genitally with a human strain of Chlamydia trachomatis

Progesterone-treated C3H and TO mice were inoculated genitally with a human C. trachomatis strain, serovar E, designated N.I. 1 or with 2SP control medium. Of the C3H mice serving as controls 93% had litters by the end of a 6-month period compared to 31% of mice infected with chlamydiae. This infertility could not be explained by tubal occlusion, since the oviducts appeared normal at autopsy. Some of the mice were induced to superovulate. Eggs were never recovered from the oviducts on the inoculated sides of infertile mice although they were sometimes found in the lumen of the uninoculated oviducts. In contrast, eggs were recovered routinely from both oviducts of control mice. In addition, eggs and/or their accompanying cumulus cells could be seen in the periovarial space of mice inoculated with chlamydiae, indicating a failure of the transportation of eggs to the oviduct. This could explain the high incidence of ectopic pregnancies in women after chlamydial infection. No adverse effect on fertility was seen in TO mice inoculated genitally with strain N.I.1. Of the mice given 2SP medium, 73% had litters, but 87% of the mice inoculated with chlamydiae were also fertile. There was, however, a significantly greater variation in the birth weights of mice born to infected TO mothers than those born to control mice. This difference in the susceptibility of mouse strains suggests that a genetic predisposition should also be considered for man.     

Seasonal variation in fertility, fecundity and litter sex ratio in laboratory and wild stocks of house mice (Mus domesticus)

Data compilations were made for three parameters pertaining to reproduction in a domestic strain (14 years) and a wild stock (4 years) of commensal house mice: (a) the percentage of females mated that produced litters; (b) the average number of pups per litter; and (c) the sex ratio of the pups in the litters. Fecundity and fertility varied seasonally in both domestic and wild mice. More females become pregnant and litter sizes were larger in the spring, summer, and fall months than during the winter season. Sex ratios also varied seasonally with more male biased litters produced during the 4 winter months. There appear to be seasonal shifts in productivity for both stocks of mice and these seasonal trends have not been altered by domestication under laboratory conditions. In spite of the fact that house mice are generally opportunistic, it is possible that there has been selection in the mice for shifting rates of production in relation to the best seasons of the year in terms of climate and resource availability. The higher production of males during summer months may be geared toward greater success in dispersal at that season and a higher probability that the males can find a territory and mate successfully in summer rather than winter. These results have potential implications for animal breeders and for those who maintain mouse colonies to produce animals for scientific investigations.     

Strain differences in activity and emotionality do not account for differences in learning and memory performance between C57BL/6 and DBA/2 mice

This study examined emotionality, activity, learning and memory, as well as the influence of emotionality and activity on learning and memory performance in C57BL/6 and DBA/2 mice using a mouse-test battery. DBA/2 mice performed more poorly than C57BL/6 mice in complex learning tasks such as the water maze and object recognition tasks. In contrast, C57BL/6 mice showed attenuated habituation to novelty in the open field apparatus and poorer performance in the step-down passive avoidance task. The C57BL/6 mice were less exploratory and more anxious than the DBA/2 mice. The anxiety score (open arm entries in the elevated plus maze) was significantly correlated with all measures of learning and memory in the object recognition task, and some measures in the passive avoidance and water maze tasks. Analysis of covariance (with open arm entries as a covariate) revealed that some measures on trial 1 of the object recognition task, but not the memory scores on trial 2, were confounded by anxiety. No confounding factors of anxiety were found in the water maze or passive avoidance tasks. Similar results were obtained with the activity scores (line crossing and rearing in the open field). In conclusion, strain differences in activity and anxiety did not account for strain differences in learning and memory performance of C57BL/6 and DBA/2 mice. Nonetheless, the importance of using complete behavioural test batteries should be stressed to ensure that strain differences in learning and memory tasks are not confounded by non-cognitive factors.     

Resistance to Naegleria fowleri infection passively acquired from immunized splenocyte, serum or milk

A pathogenic free-living amoeba, Naegleria fowleri, causes primary amoebic meningoencephalitis to human and experimental animals. This infection is rare, but the mortality is very high. Nowadays, drug treatment or active immunization of human or mice are being tried with partial effectiveness. This study shows passive immunization effect by transfer of immunized spleen cells, serum, or milk from immunized mother in mouse experimental model. Young BALB/c mice were immunized intraperitoneally with 2-3 X 10(6) trophozoites of N. fowleri, and spleen cells and sera were collected for injection to recipient mice. There were seven transfer groups, i.e., immunized mouse serum, spleen cells, serum and spleen cells, normal mouse serum, spleen cells, serum and spleen cells, and control group. Three days later, BALB/c mice were inoculated with 1 x 10(4) trophozoites of N. fowleri intranasally. After infection, decreased mortality and prolonged survival time of mice were noted in immunized groups compared with non-immunized control group. The groups injected with immunized spleen cells or normal serum showed lower mortality than that of controls but showed no changes of serum IgG level. The groups injected with immunized serum or normal spleen cells showed increased serum IgG level after immunization but hundred percent mortality was observed. Mother mice were immunized intraperitoneally with 2-3 X 10(6) trophozoites of N. fowleri at the end of pregnancy and weaning period. Soon after the delivery, litters born of non-immunized mother were matched with immunized mother for feeding immune milk. After three weeks, the litters were infected with 1 X 10(4) trophozoites of N. fowleri or sacrificed for serum collection to measure the IgG levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex- and APOE isoform-dependent effects of radiation on cognitive function

Clinical irradiation of the brain induces hippocampus-dependent cognitive impairments in some but not all individuals, suggesting the involvement of genetic risk factors. Deficiency of apolipoprotein E (APOE), which is important for the metabolism and redistribution of lipoproteins and cholesterol, increases behavioral impairments after irradiation, supporting a protective role for APOE against radiation-induced cognitive injury. Compared to APOE3, APOE4 increases while APOE2 decreases the risk of developing age-related cognitive decline and Alzheimer's disease, particularly in women. To determine the potential effects of APOE isoform and sex on radiation-induced cognitive impairments, we irradiated 2-month-old male and female APOE2, APOE3 and APOE4 mice and assessed their cognitive performance 3 months later. When hippocampus-dependent spatial learning and memory were assessed in the water maze, sham-irradiated female APOE2, APOE3 and APOE4 and irradiated female APOE2 mice showed spatial memory retention, but irradiated female APOE3 and APOE4 mice did not. Compared to sham-irradiated female APOE4 mice, irradiated female APOE4 mice also required more trials to reach criterion in the hippocampus-dependent passive avoidance test. Radiation had no effects on water maze or passive avoidance learning and memory of male APOE2, APOE3 or APOE4 mice, indicating that the effects of radiation on cognitive performance are dependent on sex- and APOE isoform.     

MATERNAL PROCESSES IN THE COLD-ADAPTATION OF MICE

• 1 Both laboratory and wild house mice, Mus musculus, given bedding, can breed in captivity in an environment kept at – 3°C. The nest temperature when a young litter is present then fluctuates widely. In a typical laboratory (at 21°C) the temperature of the nest is both higher and more constant.
• 2 The ovaries of pregnant mice breeding at – 3°C have more corpora lute a than controls at 21°C. This is not an index of a higher ovulation rate, but is evidently due to the presence of corpora lutea from a pievious ovulation.
• 3 In the absence of concurrent lactation, weights and numbers of foetuses at the sixteenth day of gestation are little affected by cold; but in both environments foetal weight diminishes with increasing size of litter. This is a systemic effect: foetal weight is hardly if at all influenced by the number of other foetuses in the same uterine horn.
• 4 Cold delays the onset of breeding and lengthens the interval between litters. Mean litter sizes are usually lower than in the warm environment, mainly through absence of large litters.
• 5 The body weights of laboratory mice are usually lower at – 3°C than 21°C at all ages from 3 weeks. This does not, however, apply to strain C57BL, which never stores much fat in adipose tissue. Wild mice bred at – 3°C are heavier than controls at 21°C, possibly because only the heavier individuals survive in early life.
• 6 F ₁ hybrids produced by crossing two inbred strains breed better and more consistently than the parent strains at both temperatures; but the effect of heterozygosis is much greater in the cold environment.
• 7 Food intake changes little during pregnancy, but rises greatly during the first 10 days of lactation at both temperatures.
• 8 At 21°C, body weight, excluding the weight of the litter, increases only slightly during pregnancy; but the weights of the heart and liver are greatly increased. The weight of the stomach also rises; the small intestine lengthens, but becomes lighter. During lactation the liver becomes still heavier, and the small intestine more than restores its loss of weight. The kidneys also become heavier. At – 3°C similar changes occur, but the heart is heavier at all stages of the reproductive cycle than it is at 21°C. The kidneys, too, are consistently heavier in the cold, and so is the small intestine. By contrast, the liver of pregnant or lactating females at – 3°C is no heavier than in the warm environment.
• 9 Pregnancy entails an increase in the absolute amount of nitrogen in the body, in both environments; but females at – 3°C have less nitrogen and collagen than controls. Pregnancy does not alter body fat at either temperature, but lactation is accompanied by some loss. At birth, mice born in the cold environment have more than twice as much body fat as controls.
• 10 When mice are bred for their full reproductive span, the effect of a cold environment depends markedly on genotype. Mice of strain A2G/Tb eventually produce as many young in the cold environment as in the warm, but take longer to do so; C57BL/Tb produce fewer young, Wild mice produce fewer litters at – 3°C, and have a much higher nestling mortality. Most of the mortality is due to loss of whole litters.
• 11 The preceding statements apply to mice of the first two or three generations in a cold environment, There are further effects of breeding for many generations in the cold. Wild mice bred for ten generations lose fewer litters in later than in earlier generations. After ten generations, some wild mice were moved from –3 to 21°C. Their reproductive performance was then much superior to that of controls which had been kept at 21°C throughout. The transferred mice were also quicker than the controls to make a nest of paper.
• 12 Genetically heterogeneous laboratory mice, after twelve generations in the cold, were similarly returned to the warm environment. Their offspring were heavier than controls; but there was no superiority in reproductive performance.
• 13 A2G/Tb mice kept at –3°C, though highly inbred, also improved in reproductive performance over a number of generations: in particular, their infant mortality declined. This was probably not due to a genetical change, but to a cumulative maternal effect.
• 14 Maternal performance was studied by cross-fostering young at birth between these ‘Eskimo’ mice, ‘immigrant’ mice of the first or second generation reared in the cold, and controls at 21°C. There was some evidence of an effect of true parentage, regardless of foster parentage, on body weight: the young of the Eskimo mice tended to be heavier than the others. There was also evidence that this influence persisted into a second generation. Mortality among the fostered young was influenced only by true parentage, not by foster parentage or environmental temperature. Some of the fostered mice were mated. Again, among their young, mortality in the nest was not affected by environmental temperature; but those whose true ancestry was Eskimo displayed a lower mortality than the others.
• 15 If a young mammal is given special treatment (such as exposure outside the nest), the treatment may influence, not only the individual treated, but also the behaviour of the parents; and the altered parental behaviour may in turn affect the development of the young. Enhanced parental attention in the nest has been directly observed after young have been exposed to cold or other treatment. It can probably accelerate maturation, and improve reproductive performance by lowering mortality among the young of the treated mice. Hence the direct effects of treatment in infancy can never be distinguished with certainty from indirect effects through changed parental behaviour, unless the experimental animals are reared artificially.
• 16 A comprehensive theory of ‘stress’, that is, of the response of a species to an environmental change for the worse, requires that attention should be paid to the following: (i) the effects of physiological (ontogenetic) adaptation to one ‘stressor’, such as cold, on response to another, such as infection; (ii) the ways in which conditions of rearing, especially early exposure to mildly adverse conditions such as lower temperature, influence later physiological, reproductive and behaviour al performance; (iii) the relationships of the above with the adaptive changes of pregnancy and lactation.

     

Lactation in mice fed endophyte-infected tall fescue seed

This study was conducted to assess the effects of endophyte-infected Acremonium coenophialum tall fescue (KY-31) seed (80% infected) on lactation in CD-1 dams and suckling performance of pups as measured by pup survival and growth rates. Twenty-four pairs of mature CD-1 mice were randomly allocated to four dietary treatments: 1) 100% mouse chow ad libitum; 2) 40% endophyte-infected tall fescue seed and 60% mouse chow (w/w); 3) reduced intake (100% chow), adjusted daily to the intake level of Treatment 2; and 4) 60% infected tall fescue seed and 40% chow. The mice were preconditioned on their respective diets for 100 d prior to 96 h of cohabitation between pairs of males and females. At parturition the litters were removed, and each dam was given a litter of six pups of equal weight, size and sex ratio to suckle for 15 days. All pups given to all the dams were born to other mice that were not part of the study and had not been exposed to endophyte-containing diets. Dams and litter weights were measured daily for 15 consecutive days. The combined body weight measurements of litters from dams fed the tall fescue containing diets (Treatments 2 and 4) were significantly lower (2.07 +/- 0.41 g/d) than that of litters from dams fed the chow containing diets (Treatments 1 and 3) during the suckling trial (P<0.05). Similarly, nine of ten (90%) dams fed the chow containing diets maintained five or more pups (5.5 +/- 0.2) throughout the study as compared to five of nine (55.6%) dams fed the tall fescue containing diets that maintained less than five pups (4.5 +/- 0.2).     

Blood changes and fertility derangements following the injection of Candida albicans into the spleen of the experimental animals (occurrence of hypersplenism)

Summary The injection ofCandida albicans (under experimental conditions used here) into the spleens of Wistar rats and Swiss mice produces profound hematological changes which are similar in rats and mice. After injection of the organisms there was steady lowering of the white cells and of the platelets in mice and in rats. Following splenectomy there was a sharp rise of both platelets and white cells in mice and rats. Mild normocytic, normochromic anemia was observed during the experiment. Following the splenectomy the level of hemoglobin returned to normal in fourteen weeks in the rats and in thirteen weeks in the mice. An increased level of reticulocytes and siderocytes was observed during the experiment. The mean value of the spleen weights in the experimental animals was higher than in the controls. Hyperplasia was the constant histological feature of these spleens. Bone marrow was either normal or hyperplastic. plastic. These changes correspond to the picture known in human pathology as hypersplenism. The injected organisms could still be cultured from the spleen about 4–6 months after operation. Attempts to isolate the injected organisms after 6 months were unsuccessful. The experimental mice showed derangement of fertility. Of the forty females mated with normal males only seven became pregnant. The litters were normal, 7–12 babies. Thirty percent of the young died before one month. Many of them showed growth retardation.This work was supported by a Damon Runyon Memorial Fund Grant No. 720.     

D-Pen2-[D-Pen5]enkephalin impairs acquisition and enhances retention of a one-way active avoidance response in rats.

We reported previously that D-Pen2-[D-Pen5]enkephalin (DPDE), a delta-opioid receptor selective analog of Leu-enkephalin, impairs acquisition of an automated jump-up avoidance response in rats and acquisition of a one-way active avoidance response in mice. In the present study we investigated the effects of DPDPE on one-way avoidance conditioning in rats. The rats received two escape-only trials on day 1 and eight additional training trials on day 2. DPDPE (1.16 micrograms/kg IP) administered prior to training on day 2 impaired acquisition of the avoidance response. On the other hand, DPDPE (0.332 microgram/kg IP) administered following presentation of the two escape-only trials on day 1 significantly enhanced retention, as measured by improved one-way active avoidance performance on day 2. These results indicate that activation of delta-opioid receptors by DPDPE has a modulatory effect on acquisition and retention of aversively motivated performance.     

Do Laboratory Mouse Females that Lose Their Litters Behave Differently around Parturition?

Efficiency in laboratory mouse breeding is hampered by poor reproductive performance, including the loss of entire litters shortly after birth. However, the underlying mechanisms are not yet fully understood and establishing the cause of death in laboratory mouse pups can be complicated. Newborn mouse pups are generally hidden in nests, dead pups are often eaten by the female, and the widespread practice of leaving periparturient females undisturbed complicates inspection, which may delay the discovery of pup loss. In order to efficiently prevent problems with litter loss, it is important to find key factors for survival. We investigated differences in periparturient behavior between female laboratory mice whose pups survived until weaning and females whose entire litters were lost. Video recordings of 82 primiparous females of the C57BL/6 strain or knockouts with C57BL/6 background were used. The mice were observed from 24 h before until 24 h after parturition and female behaviors coded using a pre-established ethogram. The relationship between behavior and survival was analyzed using logistic models, where litter survival was regressed on the proportion of 30-s observations with at least one occurrence of the behavior. We found that females with surviving litters performed more nest building behavior during the last 24 h before parturition (p = 0.004) and spent less time outside the nest during the entire observation period (p = 0.001). Increased litter survival was also associated with more passive maternal behaviors and the female ignoring still pups less. Females that lost their litters performed more parturition-related behaviors, suggesting prolonged labor. The results indicate that maternal behavior plays a significant role in laboratory mouse pup survival. Complications at parturition also contribute to litter mortality.     

Omega-3 fatty acids deprivation affects ontogeny of glutamatergic synapses in rats: Relevance for behavior alterations

Essential omega-3 polyunsaturated fatty acids (ω3) are crucial to brain development and function, being relevant for behavioral performance. In the present study we examined the influence of dietary ω3 in the development of the glutamatergic system and on behavior parameters in rats. Female rats received isocaloric diets, either with ω3 (ω3 group) or a ω3 deficient diet (D group). In ontogeny experiments of their litters, hippocampal immunocontent of ionotropic NMDA and AMPA glutamatergic receptors subunits (NR2 A\B and GluR1, respectively) and the alpha isoform of the calcium-calmodulin protein kinase type II (αCaMKII) were evaluated. Additionally, hippocampal [³H]glutamate binding and uptake were assessed. Behavioral performance was evaluated when the litters were adult (60 days old), through the open-field, plus-maze, inhibitory avoidance and flinch-jump tasks. The D group showed decreased immunocontent of all proteins analyzed at 02 days of life (P2) in comparison with the ω3 group, although the difference disappeared at 21 days of life (except for αCaMKII, which content normalized at 60 days old). The same pattern was found for [³H]glutamate binding, whereas [³H]glutamate uptake was not affected. The D group also showed memory deficits in the inhibitory avoidance, increased in the exploratory pattern in open-field, and anxiety-like behavior in plus-maze. Taken together, our results suggest that dietary ω3 content is relevant for glutamatergic system development and for behavioral performance in adulthood. The putative correlation among the neurochemical and behavioral alterations caused by dietary ω3 deficiency is discussed.     

Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer's disease

It has become generally accepted that new neurones are added and integrated mainly in two areas of the mammalian CNS, the subventricular zone and the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus, which is of central importance in learning and memory. The newly generated cells display neuronal morphology, are able to generate action potentials and receive functional synaptic inputs, i.e. their properties are similar to those found in mature neurones. Alzheimer's disease (AD) is the primary and widespread cause of dementia and is an age-related, progressive and irreversible neurodegenerative disease that deteriorates cognitive functions. Here, we have used male and female triple transgenic mice (3xTg-AD) harbouring three mutant genes (beta-amyloid precursor protein, presenilin-1 and tau) and their respective non-transgenic (non-Tg) controls at 2, 3, 4, 6, 9 and 12 months of age to establish the link between AD and neurogenesis. Using immunohistochemistry we determined the area density of proliferating cells within the SGZ of the DG, measured by the presence of phosphorylated Histone H3 (HH3), and their possible co-localisation with GFAP to exclude a glial phenotype. Less than 1% of the HH3 labeled cells co-localised with GFAP. Both non-Tg and 3xTg-AD showed an age-dependent decrease in neurogenesis. However, male 3xTg-AD mice demonstrated a further reduction in the production of new neurones from 9 months of age (73% decrease) and a complete depletion at 12 months, when compared to controls. In addition, female 3xTg-AD mice showed an earlier but equivalent decrease in neurogenesis at 4 months (reduction of 63%) with an almost inexistent rate at 12 months (88% decrease) compared to controls. This reduction in neurogenesis was directly associated with the presence of beta-amyloid plaques and an increase in the number of beta-amyloid containing neurones in the hippocampus; which in the case of 3xgTg females was directly correlated. These results suggest that 3xTg-AD mice have an impaired ability to generate new neurones in the DG of the hippocampus, the severity of which increases with age and might be directly associated with the known cognitive impairment observed from 6 months of age onwards . The earlier reduction of neurogenesis in females, from 4 months, is in agreement with the higher prevalence of AD in women than in men. Thus it is conceivable to speculate that a recovery in neurogenesis rates in AD could help to rescue cognitive impairment.