In recent years, next-generation sequencing (NGS) technologies targeting the microRNA (miRNA) transcriptome revealed the existence of tRNA-derived short RNAs: tRNA halves (tiRNAs) and tRNA-derived fragments (tRFs). These small RNAs represent a noveltype of small non-coding RNAs (sncRNAs), which are heterogeneous in size, nucleotide composition and biogenesis, and have been suggested to be involved in translation, cell proliferation, priming of viral reverse transcriptases, regulation of gene expression, modulation of the DNA damage response, tumor suppression and neurological disorders. Herein, we review the mechanism of their biogenesis and discuss in detail the regulatory roles they play in cell physiology. We also point out that the biological function of tRNA-derived short RNAs will be understood better as research moves forward, and that this knowledge will find its way into clinical application in the near future.

Understanding the role of adult neural stem cells in maintaining specific brain function is a rapidly expanding research field. Recent technological advances to culture and trace neural stem cells, such as stem cell isolation and expansion and inducible transgenic lineage tracing mouse models, have enabled more in-depth studies into the mechanisms governing neural stem cell homeostasis and pathophysiology in the adult brain. In this review we will briefly discuss the types and locations of adult neural stem cells in the ammalian brain, recent developments in tools used to study these cells, and the translational implications.

Injury in the central nervous system (CNS), stroke in the brain and trauma in the spinal cord in particular, may result in permanent disability of the patients, since CNS axons do not regenerate appreciably in their native environment due to several inhibitory molecules in the extracellular environment. Therefore,no effective clinical therapies so far are convincingly accepted for CNS injuries. Tissue engineering strategies employing biomaterials are now considered as a promising approach for restoration of these injuries, and hydrogel-based biomaterials are widely employed in this field. Among them, many studies have proven that hyaluronic acid (HA) hydrogel is a reliable and effective biomaterial, which can be a well compatible scaffold with CNS tissue and creating a good microenvironment of neural regeneration in the CNS tissue. The aim of this review is to outline how to use HA-based scaffolds to build up a suitable microenvironment of neural regeneration and restoration after CNS injury, and thereby to indicate the HA hydrogel is a promising scaffold for restoration in the CNS.

Mammalian brain circuits consist of dynamically interconnected neurons with characteristic morphology, physiology, connectivity and genetics which are often called neuronal cell types. Neuronal cell types have been considered as building blocks of brain circuits, but knowledge of how neuron types or subtypes connect to and interact with each other to perform neuralcomputation is still lacking. Such mechanistic insights are critical not only to our understanding of normal brain functions, such as perception, motion and cognition, but also to brain disorders including Alzheimer’s disease, Schizophrenia and epilepsy, to name a few. Thus it is necessary to carry out systematic and standardized studies on neuronal cell-type specific mechanisms for brain circuit organization and function, which will provide good opportunities to bridge basic and clinical research. Here based on recent technology advancements,we discuss the strategy to target and manipulate specific populations of neurons in vivo to provide unique insights on how neuron types or subtypes behave, interact, and generate emergent properties in a fully connected brain network. Our approach is highlighted by combining transgenic animal models, targeted electrophysiology and imaging with robotics, thus complete and standardized mapping of in vivo properties of genetically defined neuron populations can be achieved in transgenic mouse models, which will facilitate the development of novel therapeutic strategies for brain disorders.

To facilitate live imaging of demyelination and remyelination, we have generated a Xenopus laevis transgenic line, MBP-GFP-NTR, allowing conditional ablation of myelinating oligodendrocytes. In this line, the proximal portion of mouse myelin basic protein (MBP) regulatory sequence, specific to mature myelin-forming oligodendrocytes, drives the expression of a transgene protein formed by the GFP reporter fused to the Escherichia coli nitroreductase (NTR) selection enzyme. The NTR enzyme converts the innocuous prodrug metronidazole (MTZ) to a cytotoxin. The demyelination response of MBP-GFP-NTR tadpoles to MTZ is followed by spontaneous remyelination after cessation of MTZ treatment. Thanks to the transparency of tadpoles,these events can be monitored in vivo by two-photon imaging and easily quantified on a simple fluorescence macroscope. We have used the MBP-GFP-NTR model to screen in vivo molecules favoring remyelination. At the end of MTZ-induced demyelination, tadpoles were switched to water containing the compounds to be tested.After 3 days of treatment remyelination was assayed by counting the number of GFP+ oligodendrocytes per optic nerve. Using Crispr/Cas9 strategy, the target of the candidate molecule can be easily deleted in the MBPGFP-NTR line to examine the mechanism of action of the candidate molecule. Therefore the Xenopus laevis transgenic line, MBP-GFP-NTR, allowing conditional ablation of myelinating oligodendrocytes, constitutes a new medium-throughput screening platform for myelin repair therapeutics in demyelinating diseases.