Cell-permeable proteins are emerging as unconventional regulators of signal transduction and providing a potential for therapeutic applications. However, only a few of them are identified and studied in detail. We identify a novel cell-permeable protein, mouse LLP homolog (mLLP), and uncover its roles in regulating neural development. We found that mLLP is strongly expressed in developing nervous system and that mLLP knockdown or overexpression during maturation of cultured neurons affected the neuronal growth and synaptic transmission. Interestingly, extracellular addition of mLLP protein enhanced dendritic arborization, demonstrating the non-cell-autonomous effect of mLLP. Moreover, mLLP interacts with CCCTC-binding factor (CTCF) as well as transcriptional machineries and modulates gene expression involved in neuronal growth. Together, these results illustrate the characteristics and roles of previously unknown cell-permeable protein mLLP in modulating neural development.
Fear conditioning has been used to study pathogenic mechanisms underlying anxiety disorders. Several studies have shown that humans with anxiety disorders exhibit strong fear responses during the acquisition of conditioned fear. However, there have been no studies investigating whether basal anxiety within the normal range is related to conditioned fear in rodents. We hypothesized that individual differences in conditioned fear are correlated to the basal anxiety level of each individual. To test this hypothesis, we measured the basal anxiety of mice by using the elevated-plus maze (EPM) and open field test (OFT) and correlated these data with contextual freezing during contextual fear conditioning (CFC). Strong correlation was found between the basal anxiety level measured in the OFT and contextual freezing in the CFC. Baseline freezing was also strongly correlated with the contextual freezing level during the retrieval phase of CFC. However, the basal anxiety level measured in the EPM was correlated neither with conditioned fear nor with baseline freezing in the CFC. These results suggest that both basal anxiety in the OFT and baseline freezing are related to contextually conditioned fear.
Food deprivation can affect performance on difficult cognitive task, such as the delayed nonmatch-to-place T-maze task (DNMT). The importance of food deprivation on maintaining high motivation for DNMT task has been emphasized, but not many studies have investigated the optimal conditions for depriving rodents to maximize performance. Establishing appropriate conditions for food deprivation is necessary to maintain DNMT task motivation. We applied different conditions of food deprivation (1-h food restriction vs. 1.5-g food restriction; single caging vs. group caging) and measured body weight and the number of correct choices that 8-week-old C57BL/6J mice made during the DNMT task. The 1.5-g food restriction group maintained 76.0±0.6% of their initial body weight, but the final body weight of the 1-h food restriction condition group was reduced to 62.2±0.8% of their initial body weight. These results propose that 1.5-g food restriction condition is effective condition for maintaining both body weight and motivation to complete the DNMT task.
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