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The calcium dysregulation hypothesis of brain aging posits that an age-related increase in neuronal calcium concentration is responsible for alterations in a variety of cellular processes that ultimately result in learning and memory deficits in aged individuals. We previously generated a novel transgenic mouse line, in which expression of the L-type voltage-gated calcium, CaV1.3, is increased by ~50% over wild-type littermates. Here, we show that, in young mice, this increase is sufficient to drive changes in neuronal physiology and cognitive function similar to those observed in aged animals. Specifically, there is an increase in the magnitude of the postburst afterhyperpolarization, a deficit in spatial learning and memory (assessed by the Morris water maze), a deficit in recognition memory (assessed in novel object recognition), and an overgeneralization of fear to novel contexts (assessed by contextual fear conditioning). While overexpression of CaV1.3 recapitulated these key aspects of brain aging, it did not produce alterations in action potential firing rates, basal synaptic communication, or spine number/density. Taken together, these results suggest that increased expression of CaV1.3 in the aged brain is a crucial factor that acts in concert with age-related changes in other processes to produce the full complement of structural, functional, and behavioral outcomes that are characteristic of aged animals.  相似文献   

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DNA methylation is one of the essential factors in the control of gene expression. Alteration of the DNA methylation pattern has been linked to various neurological, behavioral and neurocognitive dysfunctions. Recent studies have pointed out the importance of epigenetics in brain development and functions including learning and memory. Nutrients related to one‐carbon metabolism are known to play important roles in the maintenance of genomic DNA methylation. Previous studies have shown that the long‐term administration of a diet lacking essential one‐carbon nutrients such as methionine, choline and folic acid (methyl donors) caused global DNA hypermethylation in the brain. Therefore, the long‐term feeding of a methyl‐donor‐deficient diet may cause abnormal brain development including learning and memory. To confirm this hypothesis, 3‐week‐old mice were maintained on a folate‐, methionine‐ and choline‐deficient (FMCD) or control (CON) diet for 3 weeks. We found that the methyl‐donor deficiency impaired both novel object recognition and fear extinction after 3 weeks of treatment. The FMCD group showed spontaneous recovery of fear that differed from that in CON. In addition, we found decreased Gria1 gene expression and specific CpG hypermethylation of the Gria1 promoter region in the FMCD hippocampus. Our data suggest that a chronic dietary lack of methyl donors in the developmental period affects learning, memory and gene expressions in the hippocampus.  相似文献   

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Oona Poranen  Suvi Ruuskanen 《Ibis》2021,163(1):247-252
The pace‐of‐life syndrome hypothesis (POLS) represents an attractive theoretical framework suggesting that physiological and behavioural traits have evolved together with environmental conditions and life‐history strategies. POLS predicts that metabolic differences covary with behavioural variation such that high metabolic rate is associated with risk‐prone behaviour and a faster pace‐of‐life, whereas a low metabolic rate is associated with risk‐averse behaviour and a slower pace‐of‐life. We tested the POLS hypothesis in captive European Pied Flycatchers during their first year by examining the relationship between explorative behaviour and basal metabolic rate. Our results are inconsistent with POLS. The positive association of explorative behaviour with basal metabolic rate was not recovered for either sex, possibly due to foraging conditions in the aviaries where control and trial groups were fed twice a day, the birds' young age, developmental plasticity, or a non‐existent syndrome.  相似文献   

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Swimming speed and percentage of time fish swam along the boundary of an aquarium gradually decreased with the time following release of juvenile guppies into unfamiliar surroundings. When swimming speed was plotted against time on a log scale, two distinct phases were identified. The high activity phase lasted c, 3 h in 30-day-old guppies, 6 h in 10-day-olds and not less than S h in 3-day-olds. Observed trends in swimming in guppies are interpreted as a component of exploratory behaviour. Alternating the surroundings confirmed the exploratory role of such swimming and suggested that a period of general exploration was followed by a period of more detailed investigation of habitat. An interaction between exploratory and avoidance (fear) responses is discussed.  相似文献   

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A common feature of several psychiatric disorders is the attentional impairment. eEF2K ?/?, IL1RAPL1 ?/? and SHANK3Δ11 ?/? mice were used as animal models consistently linked to changes in synaptic plasticity, learning and memory. All knockout (KO) mice and their corresponding littermates were submitted to the novel object recognition (NOR) and visual object recognition (VOR) tasks. In the NOR, eEF2K?/? mice exhibited a normal performance in terms of mean discrimination index, while SHANK3Δ11?/? and IL1RAPL1 ?/? mice were impaired when a delay of 2 and 24 hours was introduced. Surprisingly, when submitted to VOR, where the two objects were replaced with two shapes delivered from two iPods, all the mutant mice performed worse than those in the NOR. In VOR, the application of motion to different shapes, to increase attention, improved performance in eEF2K ?/? and IL1RAPL1 ?/? but not in SHANK3Δ11 ?/? mice. In SHANK3Δ11 ?/? mice, attentional deficit was also present even if different motions were applied to the same shapes or when these mice were repeatedly exposed for 5 days to the context. Behavioral analysis showed that eEF2K?/? and IL1RAPL1 ?/? mice had a good flexibility tested in the T‐maze. eEF2K?/? showed normal self‐grooming. On the basis of previous literature data indicating that SHANK3Δ11 ?/? showed impaired flexibility and reduced sociability, we identified in this genotype the most exhaustive model showing all the core symptoms of autism spectrum disorder including a heavy visual attention deficit. These findings show the importance of VOR to identify mouse models of autism.  相似文献   

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Rett syndrome (RTT) is a regressive developmental disorder characterized by motor and breathing abnormalities, anxiety, cognitive dysfunction and seizures. Approximately 95% of RTT cases are caused by more than 200 different mutations in the X‐linked gene encoding methyl‐CpG‐binding protein 2 (MeCP2). While numerous transgenic mice have been created modeling common mutations in MeCP2, the behavioral phenotype of many of these male and, especially, female mutant mice has not been well characterized. Thorough phenotyping of additional RTT mouse models will provide valuable insight into the effects of Mecp2 mutations on behavior and aid in the selection of appropriate models, ages, sexes and outcome measures for preclinical trials. In this study, we characterize the phenotype of male and female mice containing the early truncating MeCP2 R168X nonsense point mutation, one of the most common in RTT individuals, and compare the phenotypes to Mecp2 null mutants. Mecp2R168X mutants mirror many clinical features of RTT. Mecp2R168X/y males exhibit impaired motor and cognitive function and reduced anxiety. The behavioral phenotype is less severe and with later onset in Mecp2R168X/+ females. Seizures were noted in 3.7% of Mecp2R168X mutant females. The phenotype in Mecp2R168X/y mutant males is remarkably similar to our previous characterizations of Mecp2 null males, whereas Mecp2R168X/+ females exhibit a number of phenotypic differences from females heterozygous for a null Mecp2 mutation. This study describes a number of highly robust behavioral paradigms that can be used in preclinical drug trials and underscores the importance of including Mecp2 mutant females in preclinical studies .  相似文献   

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Correlations between behavioural traits constrain animals to a limited range of behavioural choices and set a limit to the available variation in behavioural phenotype of a population. These constraints are especially important during stressful situations, potentially limiting the ability to cope with stress appropriately. As yet, very little consideration has been given to a possible role for sexual selection in maintaining differences in behavioural stability within individuals: sex‐specific differences in behavioural correlations have been seldom studied, especially in the wild. In this field study, we investigated associations between neophobia (latency to enter nest in the presence of a novel object), nest defence (response to a model predator) and breathing rate in response to handling in breeding pied flycatchers (Ficedula hypoleuca). We did not find any significant difference in antipredator responses between males and females, which indicates low sexual conflict over parental care in the pied flycatcher. However, females were more neophobic than males, while males and females did not differ in their breathing rates. Further, our study demonstrated a strong positive correlation between nest defence behaviour and neophobia in male, but not in female pied flycatchers. Males that defended their nest more had lower breathing rate and higher latency to resume nestling feeding after encountering a predator decoy than males that mobbed less intensely. We found only weak evidence that nest partners might affect each other's behaviour in these contexts.  相似文献   

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Behaviour traits of cattle have been reported to affect important production traits, such as meat quality and milk performance as well as reproduction and health. Genetic predisposition is, together with environmental stimuli, undoubtedly involved in the development of behaviour phenotypes. Underlying molecular mechanisms affecting behaviour in general and behaviour and productions traits in particular still have to be studied in detail. Therefore, we performed a genome‐wide association study in an F2 Charolais × German Holstein cross‐breed population to identify genetic variants that affect behaviour‐related traits assessed in an open‐field and novel‐object test and analysed their putative impact on milk performance. Of 37 201 tested single nucleotide polymorphism (SNPs), four showed a genome‐wide and 37 a chromosome‐wide significant association with behaviour traits assessed in both tests. Nine of the SNPs that were associated with behaviour traits likewise showed a nominal significant association with milk performance traits. On chromosomes 14 and 29, six SNPs were identified to be associated with exploratory behaviour and inactivity during the novel‐object test as well as with milk yield traits. Least squares means for behaviour and milk performance traits for these SNPs revealed that genotypes associated with higher inactivity and less exploratory behaviour promote higher milk yields. Whether these results are due to molecular mechanisms simultaneously affecting behaviour and milk performance or due to a behaviour predisposition, which causes indirect effects on milk performance by influencing individual reactivity, needs further investigation.  相似文献   

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Although prominent examples exist of non-native species causing substantial ecological harm, many have neutral or positive effects, including filling surrogate roles once performed by extinct native organisms. We tested the ecological roles of two non-native mammals as seed dispersers or seed predators in Guåhan, which, due to invasive brown tree snakes (Boiga irregularis), is devoid of native seed dispersers–birds and bats. We conducted feeding trials with captive rats (Rattus spp.), which are present but uncommon due to predation by snakes, and pigs (Sus scrofa), which are abundant. We examined if and how they interacted with common forest fruits. We then compared how any gut-passed or animal-handled seeds germinated compared to seeds left in whole fruit or depulped seeds. Rats and pigs interacted with most of the fruits and seeds (>80%) that they were fed. Of those, most seeds were destroyed—78% for rats and 90% for pigs, across both native and non-native plant species. Compared to seeds germinating within whole fruits, rats improved germination of the seeds that they handled without ingesting, while pigs diminished the germination of seeds that they handled. The small percentage of seeds (approximately 1.5% for rats and 5% for pigs) that survived gut passage germinated in higher proportions than those in whole fruits. Percentages of seed survival to germination are lower than found in similar studies with native avian frugivores. Our results indicate that pigs and rats have mixed effects on seeds, but are not suitable surrogates for native seed dispersers.  相似文献   

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While many species of animals can solve food-baited problems, most studies are conducted in captivity, which may not reflect the natural behavioural and cognitive abilities of wild animals. As few studies have explored problem solving of Australian animals generally, we investigated the problem solving abilities of native Australian species in natural rainforest in the Wet Tropics of Queensland. We baited multiple types of puzzles (matchbox task, cylinder task, and tile and lever tasks on a Trixie Dog Activity Board) with different food types (seeds, fruit, sardines) and placed the puzzles in front of trail cameras. We noted the species captured on camera, whether or not individuals interacted with the puzzles, the number of interactions with puzzles, and whether or not different animals solved them. We found that seven species from multiple taxa (mammals, birds, reptiles) could solve food-baited problems in the wild, providing the first evidence of problem solving in these native species. As problem solving may help animals cope with anthropogenic threats, these results provide some insights into which Wet Tropics species may potentially be more vulnerable and which ones might be better at coping with changing conditions.  相似文献   

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Three commercially available test systems for the identification of anaerobic bacteria were evaluated for the identification of 18 proteolytic group I and 69 non-proteolytic group II Clostridium botulinum, four Clostridium sporogenes and 18 non-toxigenic group II C. botulinum-like strains. All proteolytic C. botulinum strains were misidentified by the Rapid ID 32 A and RapID ANA II, while 14 strains and all C. sporogenes strains were identified as C. botulinum or C. sporogenes by the API 20 A. Reversely, all non-proteolytic C. botulinum strains were misidentified by the API 20 A while the Rapid ID 32 A recognized 67 and RapID ANA II 68 strains. All C. sporogenes strains were recognized by the RapID ANA II, while the Rapid ID 32 A recognized one strain. All non-proteolytic non-toxigenic strains were identified as C. botulinum group II by the Rapid ID 32 A, 17 strains by the RapID ANA II, and one strain by the API 20 A. The results show that these test systems do not provide a reliable method for identification of C. botulinum.  相似文献   

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Guanylyl cyclase C (GC‐C) is found in brain regions where dopamine is expressed. We characterized a mouse in which GC‐C was knocked out (KO) that was reported to be a model of attention deficit hyperactivity disorder (ADHD). We re‐examined this model and controlled for litter effects, used 16 to 23 mice per genotype per sex and assessed an array of behavioral and neurochemical outcomes. GC‐C KO mice showed no phenotypic differences from wild‐type mice on most behavioral tests, or on striatal or hippocampal monoamines, and notably no evidence of an ADHD‐like phenotype. KO mice were impaired on novel object recognition, had decreased tactile startle but not acoustic startle, and females had increased latency on cued training trials in the Morris water maze, but not hidden platform spatial learning trials. Open‐field activity showed small differences in females but not males. The data indicate that the GC‐C KO mouse with proper controls and sample sizes has a moderate cognitive and startle phenotype but has no ADHD‐like phenotype.  相似文献   

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Animal behaviour can lead to varying levels of risk, and an individual's physical condition can alter the potential costs and benefits of undertaking risky behaviours. How risk-taking behaviour depends on condition is subject to contrasting hypotheses. The asset protection principle proposes that individuals in better condition should be more risk averse, as they have higher future reproductive potential (i.e. more to lose). The state-dependent safety hypothesis proposes that high-condition individuals that are more likely to survive and maximise the benefits of risky situations may make apparently riskier choices, as their individual risk is in fact lower. We systematically searched for studies that experimentally manipulated animals’ nutritional or energetic condition through diet treatments, and subsequently measured risk-taking behaviour in contexts relating to predation, novelty and exploration. Our meta-analysis quantified condition effects on risk-taking behaviour at both the mean and variance level. We preregistered our methods and hypotheses prior to conducting the study. Phylogenetic multilevel meta-analysis revealed that the lower-nutritional-condition individuals showed on average ca. 26% greater tendency towards risk than high-condition individuals (95% confidence interval: 15–38%; N = 126 studies, 1297 effect sizes). Meta-regressions revealed several factors influencing the overall effect, such as the experimental context used to measure risk-taking behaviour, and the life stage when condition was manipulated. Meta-analysis of variance revealed no clear overall effect of condition on behavioural variance (on average ca. 3% decrease in variance in low- versus high-condition groups; 95% confidence interval: −8 to 3%; N = 119 studies, 1235 effect sizes), however, the experimental context was an important factor influencing the strength and direction of the variance effect. Our comprehensive systematic review and meta-analysis provide insights into the roles of state dependency and plasticity in intraspecific behavioural variation. While heterogeneity among effect sizes was high, our results show that poor nutritional state on average increases risk taking in ecological contexts involving predation, novelty and exploration.  相似文献   

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Abnormally active glycogen synthase kinase‐3 (GSK3) contributes to pathological processes in multiple psychiatric and neurological disorders. Modeled in mice, this includes increasing susceptibility to dysregulation of mood‐relevant behaviors, impairing performance in several cognitive tasks and impairing adult hippocampal neural precursor cell (NPC) proliferation. These deficits are all evident in GSK3α/β knockin mice, in which serine‐to‐alanine mutations block the inhibitory serine phosphorylation regulation of both GSK3 isoforms, leaving GSK3 hyperactive. It was unknown if both GSK3 isoforms perform redundant actions in these processes, or if hyperactivity of one GSK3 isoform has a predominant effect. To test this, we examined GSK3α or GSK3β knockin mice in which only one isoform was mutated to a hyperactive form. Only GSK3β, not GSK3α, knockin mice displayed heightened vulnerability to the learned helplessness model of depression‐like behavior. Three cognitive measures impaired in GSK3α/β knockin mice showed differential regulation by GSK3 isoforms. Novel object recognition was impaired in GSK3β, not in GSK3α, knockin mice, whereas temporal order memory was not impaired in GSK3α or GSK3β knockin mice, and co‐ordinate spatial processing was impaired in both GSK3α and GSK3β knockin mice. Adult hippocampal NPC proliferation was severely impaired in GSK3β knockin mice, but not impaired in GSK3α knockin mice. Increased activity of GSK3β, in the absence of overexpression or disease pathology, is sufficient to impair mood regulation, novel object recognition and hippocampal NPC proliferation, whereas hyperactive GSK3α individually does not impair these processes. These results show that hyperactivity of the two GSK3 isoforms execute non‐redundant effects on these processes.  相似文献   

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