Abstract:Learning and memory are important works of brain. Formation of memory involves a series of molecular and cellular changes which including gene transcription, de novo protein synthesis and synaptic plasticity alterations. The studies discussed here strongly indicate that various epigenetic modifications, including DNA methylation, histone modification and RNA modification, play an integral role in learning and memory, and has garnered the attention of researchers in the past decade. In this Review, we examine the involvement of different epigenetic regulators involved in memory and learning functions and provide a theoretical basis for future research.

Abstract:Gastrin-releasing peptide (GRP) is a homolog of bombesin (BB/BN) in mammals that is distributed throughout the central nervous system. GRP is an important neuromodulator in the brain that plays an important role in various physiological functions and instinctive behaviors of animals and also can regulate the advanced functions of the brain. In the nervous system, the formation, maintenance, and extinction of animal memory are associated with GRP level, especially those related to fear and anxiety, as well as synaptic plasticity change to different degrees. GRP and its receptors are also thought to be associated with the central nervous system diseases and are potential therapeutic targets. However, the relevant mechanism has not yet been clarified, and many researchers have proposed relevant hypotheses based on different experimental methods. In this paper, we review the function of GRP and its receptors on aversive emotion-driven memory, synaptic plasticity, and the mechanism in the central nervous system from the aspects of traditional pharmacology, genetics, and electrophysiology, hoping to provide new ideas for further studies on the role of GRP system in the central nervous system.

Abstract:Duration perception is important during movement, as it can help people judge the duration of events and make better predictions and preparations. In recent years, a growing number of studies have found that duration distortion in movement is influenced by motion itself. The current paper summarized the behavioral evidence of the effects of movement on duration perception from four aspects, including movement parameters, movement stages, visual motion stimuli and motion-related individual factors. Currently, extensive research has proven that motor brain structures may serve as the core neural network of subjective temporal perception. The motor system both encodes and is involved in duration perception. The theory of how movement influences duration perception can be based on the framework of the internal clock model and can be further explained by sensorimotor interference, arousal induced by the action or embodied cognition. Future research needs to consider the effects of movement on duration perception on different time scales, as well as the study paradigms and technical approaches during movement, which can better reveal how movement regulates duration perception and the internal neural mechanism. Further, according to the features of different competitive sports, future research should provide help and guidance on reducing duration perception errors in sports and enhancing the duration perception abilities of athletes.

Abstract:Lysophosphatidic acid (LPA), a set of bioactive lipid species with simple structure, is able to regulate various cellular activities, and participates in a variety of physiological and pathological processes via binding to the LPA receptors, a series of G protein coupled receptors on cellular membrane. Autotaxin (ATX) is a secretory glycoprotein with lysophosphatidase D (lysoPLD) activity to generate LPA from lysophosphatidylcholine (LPC), which is the main source of circulating LPA. Recently, increasing evidences have revealed that ATX is highly expressed in mature adipocytes and that the ATX-LPA axis plays a role in obesity and obesity-related disorder of glucose and lipid metabolism. The ATX-LPA axis has been regarded as the novel therapeutic target for obesity-related diseases. In the present paper, we will review the research progresses of ATX-LPA axis in obesity and obesity-related diseases, such as insulin resistance and nonalcoholic fatty liver disease.

Abstract:Sex differences in the brain have long been a hot topic in neuroscience. Previous studies on gender differences have focused on brain structures and functions related to higher-level cognition, but less attention has been paid to low-level sensory and perceptual systems. Recently, a growing number of studies have shown that men and women also show remarkable differences in visual processing. In this paper, we started by reviewing the behavioral and neural evidences supporting the notion of sex differences in the visual system. We then proposed two potential explanations and discussed the evolutionary benefits of sex differences in visual perception. Finally, we highlighted the importance of incorporating sex as a biological variable in visual neuroscience research, and offered a few suggestions for future studies on sex differences in the visual system.

Abstract:Calcium indicators are often used to monitor calcium signaling in cells and organelles, which include chemical calcium indicators and genetically encoded calcium indicators. With the development of technology and the continuous increase in research requirements, various versions of calcium indicators are constantly updated. The review systematically sorts out the existing calcium indicators, and introduces in detail the most widely used calcium indicators. Here, the advantages and disadvantages of existing calcium indicators are summarized, and the parts that can be optimized and improved are discussed. The aim is to provide some ideas for the further development of calcium indicator research.

Abstract:The TANK-binding kinase 1(TBK1) is a serine and threonine kinase. It plays important roles in regulating biological functions of the body, such as sequestering the innate immunity, modulating the cell selective autophagy, regulating the apoptosis, and monitoring the cell regeneration. These mechanisms emphasize that TBK1 is inseparable from tumors, which also means inhibiting the biological function of TBK1 may induce an antitumor immune response. The circle RNA (circRNA) is a novel class of the no-coding RNA with the fixed loop structure and proved to influence on many kinds of tumor, such as gastric cancer, lung cancer, colon cancer and liver cancer, attracting the widespread concern from the scholars. Recent evidence suggests TBK1 interacts with circRNA directly, affecting the developments and the differentiation of the tumor cell. These analyses have showed the interaction between TBK1 and circRNA, which can promote the formation of cytokines and chemokines in the tumor microenvironment, reflecting the great potential of them in the tumor targeted therapy. In order to analyze their interation patterns and shed new light on the tumor targeted therapy, this paper summarizes the research on TBK1 and circRNA in tumors in the past 10 years.

Abstract:The aim of this study is to elucidate the molecular mechanism of Galanin receptors type 2(GALR2)which involved in regulation of oxidative stress in the hippocampus. We used real-time PCR technique to investigate the change of GALR2 expression in hippocampus of piglets and hippocampal neurons of rats, based on the successfully constructed oxidative stress model. Real-time PCR, Western blotting and transmission electron microscopy were used to further explore the relationship between the signal pathway mediated by GALR2 and autophagy. The results showed that the transcription levels of GALR2 were up-regulated in the hippocampus of oxidative stressed piglets and rat hippocampal neurons compared with the control group (P<0.01; P<0.05). At the same time, the transcription levels of LC3, ATG5 and Beclin-1 in oxidative stressed neurons were up-regulated (P<0.05; P<0.05; P<0.01). Correlation analysis showed that GALR2 was positively correlated with LC3, ATG5 and Beclin-1 (P<0.05; P<0.05; P<0.01). The treatment with M871, a specific inhibitor of GALR2, decreased the activity of hippocampal neurons under oxidative stress (P<0.01) , increased the number of autophagosomes (P<0.01) and transcription levels of LC3, Beclin-1 and ATG5(P<0.01) , and increased the ratio of LC3-Ⅱ/actin and P62 protein level (P<0.05) , showing that the autophagy of hippocampal neurons, which was up-regulated by oxidative stress, was inhibited with the inhibition of GALR2 expression, thus weakening the resistance to oxidative damage and decreasing the viability of neurons. Simultaneously, M871 treatment also decreased the up-regulated protein level (P<0.01) and the phosphorylation level of JNK (P<0.05) in oxidative stressed neurons, indicating that JNK is the downstream target enzyme of GALR2 in hippocampal neurons under oxidative stress. However, treatment with JNK specific inhibitor SP600125 lowered the ratio of LC3-II/actin, which was up-regulated by oxidative stress (P<0.01), showing the inhibition of JNK blocks the activation of the autophagic pathway by an up-regulated GALR2 in neurons. To sum up: under oxidative stress, the up-regulated GALR2 in hippocampal neurons can activate the autophagy pathway by up-regulating JNK signal pathway, thus attenuate oxidative stress injury and protect neurons.

Abstract:Closed-loop stimulation is one of the important development directions of deep brain stimulation (DBS) that is promising for treating various brain disorders. Contrast to the conventional open-loop stimulation with continuous stimulation for long periods of time, the closed-loop stimulation usually utilizes short sequences of high-frequency pulses. However, neuronal responses to the high-frequency stimuli may change substantially in a short period of time because of the transient process at the beginning of stimulation. The change may affect the stimulation efficacy. To investigate the transient process of high-frequency stimuli, antidromic high-frequency stimulation (A-HFS) with different constant pulse frequencies as well as varying frequency was applied at the alveus of rat hippocampal CA1 region. The amplitude of antidromically-evoked population spike (APS) was used as an index to evaluate the neuronal responses to A-HFS. The results show that at the initial period of A-HFS with a constant pulse frequency of 100, 133 and 200 Hz, the APS decreased rapidly. A higher pulse frequency generated a faster attenuation of the APS. The mean amplitudes of APS decreased by more than half within less than 1 s. The mean half-value time of APS amplitude was ~0.96 s with 100 Hz A-HFS and decreased to ~0.21 s with the pulse frequency doubled to 200 Hz. With randomly-varying frequencies in the range of 100-200 Hz to tune the pulse interval in real time, the attenuation speed of neuronal responses was significantly slowed down to prolong the maintenance of the stimulation effect. These results provide clues to develop new DBS paradigms for the implementation of short closed-loop stimulations.

Abstract:Macrophage-derived foam cell transformation is considered to be an early change in the formation and development of atherosclerosis (AS). Excessive lipid accumulation in the macrophage-derived foam cell often promotes vascular intimal growth and necrosis, which leads to plaque instability and thrombosis. Recent evidence indicated that Celasrol (CeT) can significantly regulate lipid metabolism, which has potential therapeutic significance in the process of foam cell transformation. In this study, CeT treatment can reduce the accumulation of lipid droplets in lipid-loaded Raw264.7 cell in concentration-dependent manner, and up-regulate the protein expression of ABCA1 and LXRα, the key molecules of cholesterol transport in Raw264.7. In addition, the results showed that knockdown of ABCA1 promoted lipid storage, while CeT reduced intracellular lipid accumulation and up-regulated ABCA1 expression. Moreover, LC3II /I ratio was increased and p62 was decreased after treatment with CeT for 24 h. Besides, the intracellular lipid level was restored following exposure to autophagy inhibitor 3MA. In summary, CeT can reduce intracellular lipid accumulation by up-regulating LXRα / ABCA1 signal and activating autophagy of lipocytes. Therefore, further study about the role of CeT in the transformation of macrophage derived foam cells may be a promising strategy for AS therapy and underlying target for drug intervention.

Abstract:Readily releasable pool (RRP) of synaptic vesicles as the concept that defines the capacity of vesicle availability has been widely used in the study of synaptic transmission. Several approaches have been developed to determine the size of RRP by extrapolating the cumulative EPSCs corresponding to a train stimulation based on the assumption that the properties of vesicle in this pool are homogeneous. However, the estimated RRP sizes by these approaches often vary with different stimulation frequencies. The frequency dependence displays the incompletion of estimation and contradictory to the definition of RRP. Here, we proposed an improved approach to estimate RRP size. Given the replenishment rate proportional to the released part of RRP and corrected the unreleased part of RRP, we obtained a complete mathematical description of the RRP release process and derived the analytic solution. Compared with the two commonly used methods, it has been found that this scheme well describes the dynamic process of RRP, and obtains a relatively good evaluation of RRP size and release probability. This approach is not limited by the stimulation frequency and can be well applied to the cells that cannot be stimulated by high frequency.