噪声习服对听觉损伤的保护作用机制探讨

目的:探讨噪声习服对听觉损伤的保护作用机制.方法:建立噪声习服实验动物模型.采用免疫组织化学、激光扫描共聚焦显微镜(LSCM)及图像分析等技术,定量研究噪声习服后毛细胞内纤维状肌动蛋白(F-actin)、钙调蛋白(CaM)、热休克蛋白70(HSP70)的表达及游离Ca2 浓度的变化.结果:噪声暴露后毛细胞中F-actin、CaM及HSP70的表达均呈增加趋势.与噪声损伤暴露组(H组)比较,噪声习服后损伤暴露组(CH组)中F-actin和HSP70的表达均明显增多,CaM的表达具有增加趋势.声暴露后毛细胞内游离Ca2 浓度升高,噪声损伤暴露组毛细胞内游离Ca2 浓度明显高于噪声习服组(C组)和习服后损伤暴露组.结论:噪声习服使毛细胞对于其后声刺激的保护性反应增强,毛细胞内细胞骨架系统的加强及胞内钙稳态的维持在噪声习服的保护机制中具有重要意义.     

Learning and anticipatory behaviour in a “sit-and-wait” predator: The Atlantic halibut

We studied the learning capacities and anticipatory behaviour in a “sit-and-wait” predatory fish, the Atlantic halibut, Hippoglossus hippoglossus. In Experiment 1 two groups of halibut received series of light flashes (conditioned stimulus, CS) that started before delivery of food (unconditioned stimulus, US) and persisted until after food delivery, i.e. delay conditioning. Control groups received unpaired CS and US presentations. The anticipatory behaviour of delay conditioned halibut consisted mainly of take-offs towards the surface shortly after onset of the CS. In Experiment 2 six groups of halibut were trained in three trace conditioning procedures: Two groups with 20 s, two groups with 60 s and two groups with 120 s trace interval. Learning was evident in the 20 and 60 s trace groups and in one of the 120 s trace groups. In contrast to delay conditioning the anticipatory behaviour of trace conditioned halibut was characterized by subtle movements near the tank floor with orientation towards the CS. The cautious responses of halibut after trace conditioning differed markedly from what is observed in other fish species and are suggested to reflect a “sit-and-wait” foraging strategy that requires the predator to remain undetected until the prey is within lunging range.     

One-trial associative odor learning in neonatal mice

Behavior genetics studies in mice demand efficient training protocols for rapid phenotypic screening. However, the capacity of neonatal mice to form and retain associative memories has been difficult to study due to their limited sensorimotor capacities. The present study describes a method for robust, naturalistic associative learning in neonatal mice as young as 3 days old. After removal of the dam from the home cage for 2 h, preweanling CD-1 mice of ages 3, 5, and 10 days postnatal were conditioned to associate an arbitrary odorant with the suckling and milk delivery that ensued upon her return to the home cage. After a second maternal deprivation, neonates were tested on their acquired preference for that odorant. Neonates exhibited a learned preference for the conditioned odorant over a novel control odorant. No learning was observed without deprivation, that is, when the dam was removed only briefly for scenting. One-trial learning sufficed to show clear preferences for the conditioned odorant, although repeated training (three sessions over 8 days) significantly increased the expression of preference. The development of neonatal associative learning protocols requiring minimal human intervention is important for the behavioral phenotyping of mutant and transgenic strains, particularly those modeling developmental disorders.     

Nicotine and hippocampus-dependent learning

Addiction is a complex disorder because many factors contribute to the development and maintenance of addiction. One factor is learning. For example, drug-context associations that develop during drug use could facilitate drug craving upon re-exposure to contexts previously associated with drugs. Additionally, deficits in cognitive processes associated with withdrawal could precipitate relapse in attempts to ameliorate those deficits. Because addiction and learning involve common neural areas and cell signaling cascades, addiction-related changes in processes underlying plasticity may contribute to addiction. This article examines similarities between addiction and learning at the behavioral, neural, and cellular levels, with emphasis on the neural substrates underlying the effects of acute nicotine, chronic nicotine, and withdrawal from chronic nicotine on hippocampus-dependent contextual, learning.     

Preimaginal conditioning does not affect oviposition preference in the diamondback moth

Abstract.  1. In holometabolous insects, learning has been demonstrated in both larval and adult stages. Whether learning can be retained through metamorphosis from larva via pupa to adult has long been a subject of debate. The present study is designed to distinguish between preimaginal and imaginal conditioning in the diamondback moth, Plutella xylostella L. (Lepidoptera: Plutellidae) using oviposition preference tests on females exposed to various types of learning experiences during immature and adult stages.
2. Cohorts of test insects were reared from egg to pupa on an artificial diet, or on one of two host plants, Chinese cabbage, Brassica campestris L. ssp. pekinensis , and common cabbage, Brassica oleracea L. var. capitata . The ensuing females reared on the three kinds of food showed similar oviposition preference between the two plants. A brief experience of the less preferred host, common cabbage, by adults slightly increased their preference for this plant.
3. Cohorts of test insects were reared from egg to pupa on an artificial diet with or without the addition of a neem-based oviposition deterrent (Neemix^® 4.5). Larval feeding experience did not alter oviposition response to the deterrent. However, emergence conditioning and early adult learning, achieved through experience of a residue of the deterrent carried over from the larval food on pupal cuticle and cocoons, altered oviposition preference significantly.
4. The combined results revealed no evidence of preimaginal conditioning in this insect but a strong effect of emergence conditioning and early adult learning on oviposition preference.     

The temporal pattern of responding in conditioned bar-press suppression: the role of the context switch and training mode

The present study examined the temporal pattern of responding in a conditioned bar-press suppression task in rats. Rats were exposed to either a 30-s or a 120-s conditioned stimulus (CS) followed by a footshock. Training took place either while the rats were lever-pressing for water (online), or with the lever removed from the box (offline). They were then exposed to the CS while they were lever-pressing for water, either in the training context or in a different context. Bar-press suppression during the CS was constant across the duration of the CS during training, but was restricted to the initial portion of the CS at the time of testing, especially when subjects were tested in a different context. Those results replicate the reactive (as opposed to anticipatory) pattern observed in a lick suppression procedure by Jozefowiez et al. (2011) and indicate that a change in context at the time of testing might be critical for its expression.     

Proteomic analysis of mouse brain cortex identifies metabolic down-regulation as a general feature of ischemic pre-conditioning

J. Neurochem. (2012) 122, 1219-1229. ABSTRACT: The molecular mechanisms that lead to ischemic pre-conditioning are not completely understood, and proteins are important players. We compared the mouse brain cortex proteome from different ischemia sets: transient (7?min) middle cerebral artery occlusion (7'MCAo, pre-conditioning stimulus), permanent MCAo (pMCAo, severe ischemia), and pMCAo 4?days after 7'MCAo (7'MCAo/pMCAo, pre-conditioned model). Proteins were analyzed by two-dimensional electrophoresis coupled to liquid chromatography-tandem mass spectrometry. Overall, 28 proteins were expressed differentially from sham controls, and identified. The ischemic pre-conditioning stimulus alone up-regulated the stress protein heat-shock protein 70 (HSP70), possibly activated by the androgen receptor. Western blotting confirmed the increased expression of HSP70 and showed that androgen receptor expression paralleled that of HSP70. In the ischemic-tolerant group (7'MCAo/pMCAo), a number of proteins over-expressed after pMCAo returned to sham levels, seven proteins remained up-regulated as in pMCAo, and five proteins mainly involved in energy metabolism and mitochondrial electron transport and unchanged in pMCAo were down-regulated only in ischemic tolerance, suggesting a role in brain pre-conditioning. Astrocytes participated in ischemic-tolerance induction, as shown by the down-regulation of glutamine synthetase in the 7'MCAo/pMCAo group. The results suggest that metabolic down-regulation was a general feature of ischemic pre-conditioning, playing a pivotal role in neuroprotection.     

Identification of differentially expressed microRNAs and their PKC-isoform specific gene network prediction during hypoxic pre-conditioning and focal cerebral ischemia of mice

We previously reported the involvement of conventional protein kinase C (cPKC) βII, γ, novel PKC (nPKC) ε and their interacting proteins in hypoxic pre-conditioning (HPC)-induced neuroprotection. In this study, the large-scale miRNA microarrays and bioinformatics analysis were used to determine the differentially expressed miRNAs and their PKC-isoform specific gene network in mouse brain after HPC and 6?h middle cerebral artery occlusion (MCAO). We found 4 up-regulated and 13 down-regulated miRNAs in the cortex of HPC mice, 26 increased and 39 decreased gene expressions of miRNAs in the peri-infarct region of 6?h MCAO mice, and 11 up-regulated and 22 down-regulated miRNAs in the peri-infarct region of HPC and 6?h MCAO mice. Based on Diff Score, 19 differentially expressed miRNAs were identified in HPC and 6?h MCAO mouse brain. Then the miRNA-gene-network of 19 specified miRNAs target genes of cPKCβII, γ and nPKCε-interacting protein was predicted by using bioinformatics analysis of genome databases. Furthermore, the down-regulated miR-615-3p during HPC had a detrimental effect on the oxygen-glucose deprivation (OGD)-induced N2A cell injury. These results suggested that the identified 19 miRNAs, notably miR-615-3p, might target these genes of cPKCβII, γ and nPKCε-interacting proteins involved in HPC-induced neuroprotection.