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.

As a complicated cerebrovascular disorder,ischemic stroke involves a series of mind-body connections. The “stress” refers to a state of threatened homeostasis caused by any form of internal or external disturbing forces. The “stress response” is a counteracting force that neutralizes the effects of stressors and re-establish homeostasis, which may cause two different outcomes, the allostasis and allostatic load. The prompt stress system is the autonomic nervous system (ANS) with two branches the sympathetic (SNS) and parasympathetic (PNS) nervous systems that play an important role in regulating stress response. As a typical example and final endpoint of allostatic load, ischemic stroke and its complications are related to stress and autonomic dysfunction.Different clinical tests are described for assessing autonomic function in ischemic stroke. This review may bring possibilities for future study to investigate specific treatment on ANS function and stress management on the context of traditional stroke therapies, and thus help improve the clinical outcomes and prognosis of ischemic stroke.

Intracranial atherosclerotic disease (ICAD) is an important cause for ischemic stroke and transient ischemic stroke (TIA) throughout the world, especially in Asians, which is not fully appreciated, partly due to its inaccessibility and limitations of current neuroimaging methods. The computational fluid dynamics (CFD) modeling technique provides a novel approach to reveal the hemodynamic characteristics in ICAD, e.g., the distributions of pressure, wall shear stress and flow velocity.In this review article, we aim to provide an overview of the general methodology of CFD modeling in arterial stenotic diseases, the established application of this technique in coronary artery disease, and more importantly,perspectives and challenges of this technique in the investigation of ICAD. Promising findings of preliminary studies using a CFD model for hemodynamic analysis in ICAD warrant verifications. Further studies in this area will help rectify loopholes in the current secondary prevention strategy, and inform individualized treatment for ICAD patients in the near future.

Ischemic stroke is a major cause of morbidity and mortality, and currently there is no effective treatment. The family of protein kinase C (PKCs) could phosphorylate serine or threonine residues of its substrate proteins and play a key role in the ischemia/reperfusion injury. Autophagy is essential for maintaining cell homeostasis under physiological condition and acts as a double-edged sword in the process of ischemic neuronal death. In this article, we reviewed the PKCs isoform-specific signaling pathways and PKC-modulated autophagy in ischemic stroke.

Major depressive disorder (MDD) has been a devastating neurological problem in modern history.However, therapeutic strategies to relief the disease are inadequate. The limit in understanding of the molecular mechanism of MDD has been holding back discovery of new therapies. Behind this problem is the establishment of animal models to truly reflect human MDD pathology.In this review, we discuss our current understanding of the molecular mechanism of MDD and the strength and weakness of rodent models of depression. Developing new models of MDD and finding new drugable targets are still important steps to discover new therapies against MDD.

The prevalence of stroke displays obvious geographical variation and is higher on plateaus.Similarly, prolonged stay at high altitude is associated with higher incidence of stroke. High-altitude hypoxia can elicit various physiological dysfunctions, and hypoxia is suggested to be the principal contributing factor of stroke. In this brief review, the effects of hypoxia on the properties of the blood components such as erythrocytes, leukocytes and thrombocytes are presented, in an effort to inform the prevention and treatment of stroke in high-altitude areas.

As biomarkers are important in the early diagnosis of Alzheimer's disease (AD), the first collaborative work of recruiting early-onset familial AD (EOFAD) families in Canada and China was initiated in 2012. The registration networks have collected hundreds of pedigrees, for which genetic screening, neuropsychological tests and amyloid and tau imaging was used to study diagnostic biomarkers for preclinical and mild cognitive impairment (MCI) stages of AD. Besides identifying pedigrees with novel mutations in presenilins (PSENs)/amyloid precursor protein (APP), the program has benefited training of Chinese research fellows, AD clinical trials for prevention, the ethical concerns for clinical findings, and other collaborative projects with Chinese investigators. Further research of the collaborative program may facilitate the testing and clinical use of novel treatments for EOFAD and late onset AD and contribute to dementia prevention strategies in Canada and China.

Alzheimer’s disease (AD) accounts for 60% to 80% of dementia cases and is the most common cause of dementia. In the past decade, studies have shown a close association between blood pressure and AD. It is found that elevated blood pressure at midlife would increase the risk of dementia, including AD. However, there is no definitive conclusion about the relationship between elderly blood pressure and cognitive function. Abnormal pulse pressure may also increase the risk of dementia. The impact of antihypertensive drugs is inconclusive, and the mechanism of their protection of cognitive function is not clear.

With the progress in global demography of aging, dementia has become a great world health-care issue that require urgent attention and settlement. Dementia can arise from a variety of factors, such as neuronal degeneration for Alzheimer’s disease (AD), vascular risk factors and multiple infarcts for vascular dementia (VaD), and both degeneration and vascular factors for mixed dementia (MD). Pathophysiology of AD includes the amyloid and tau protein hypothesis, and inflammation-related mechanisms are also widespread mentioned. Subcortical ischemic vascular dementia (SIVD), a subtype of VaD, is commonly caused by complete or incomplete lacunar infarction of VaD pathology. MD involves both degeneration and vascular factors, and the interaction between the two results in the complication of the pathological mechanism and clinical phenotype. The clinical manifestations of AD are often divided into four stages according to the progress of the disease, while the phenotypes of SIVD usually has two categories. As for MD, the phenotypes are complex and diverse. Several clinical studies showed that its symptoms and signs are more similar to SIVD than AD. This article aims to analyze and compare the different aspects of the three kinds of dementia.

Increasing evidence in recent years suggests homocysteine (Hcy) is involved in the pathogenesis of Alzheimer’s disease (AD), and that modifying this risk factor may be an alternative approach to delaying or preventing onset of this disease. However, intervention studies suggest inconsistent effects of folic acid supplementation, with or without vitamin B12, on the prevention of incident AD. Studies with Hcy-lowering therapy show beneficial effects of B vitamins in patients with mild cognitive impairment (MCI), especially in those with high Hcy levels. Further studies are needed to confirm elevated Hcy levels as a potentially treatable risk factor for AD.

With the aging of society, dementia has become a more and more serious social problem. Alzheimer’s disease (AD) is a major cause of dementia, and there is no drug to reverse the disease progression. Donepezil is the main drug currently in symptomatic treatment. However, the efficacy of donepezil was moderate, with the patient variably responding to the treatment with donepezil. The commonest adverse events in the treatment were nausea, vomiting and diarrhea; QT prolongation rarely occurred. Many patients gave up treatment because of adverse events or lack of efficacy. Pharmacogenomics is developed on the basis of pharmacogenetics, by studying the polymorphisms in genes involved in drug metabolic enzymes, transporter and drug receptor, to guide individualized treatment. In terms of the pharmacogenomics on the efficacy of donepezil, there is no clear conclusion except CYP2D6 genotype affecting drug clearance.

Objective: To investigate functional connectivity within default mode network (DMN) and executive control network (ECN) in vascular cognitive impairment, no dementia (VCIND). Methods: Twenty-eight VCIND patients and sixteen healthy controls were recruited. A seed-based connectivity analysis was performed using data from resting-state functional magnetic resonance imaging (fMRI). Based on previous findings, posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC) were chosen as regions of interest to study these networks. One-sample t-test and two-sample t-test were used for statistical analysis. Results: Compared with the controls, the VCIND group exhibited increased functional activity in such DMN regions as the left inferior temporal gyrus, parahippocampal gyrus, and medial frontal gyrus. The VCIND group had decreased functional connectivity of DMN at right superior frontal gyrus, left mid-cingulate area, the medial part of left superior frontal gyrus, and bilateral medial frontal gyrus. The VCIND group also showed decreased functional connectivity of ECN primarily at left inferior parietal gyrus, right angular gyrus, right middle occipital gyrus, and right middle frontal cortex. Conclusions: Increased functional connectivity within DMN and decreased functional connectivity within ECN suggested dysfunction of these two networks, which might be associated with the cognitive deficits in patients with VCIND. These findings may help us understand the pathogenesis and clinical characteristics of VCIND.

Glaucoma is a chronic neurodegenerative disorder characterized by progressive damage and loss of retinal ganglion cells (RGCs). It is considered one of the leading causes of irreversible blindness in the older population. There are estimates that glaucoma will affect 80 million individuals worldwide by the end of this decade, and yet we are still not able to identify the signals and the mechanisms that trigger this neurodegenerative disease. Various hypotheses have been generated to address the causes of the progressive RGC death that characterizes the disease. Age and increased intraocular pressure (IOP) have been established as the main risk factors for the development of glaucoma. Recent studies have identified additional factors that play a role in the pathogenesis of this complex multifactorial disease, including inflammation, oxidative stress, vascular dysregulation, disrupted axonal transport of neurotrophic factors, and the release of neurotoxic agents such as glutamate, nitric oxide and free radicals. The currently approved therapies for glaucoma that seek to reduce IOP, including medications, laser treatment, and surgery, are unable to reliably stop RGC loss and functional impairment. Considering the significant personal, medical and socio-economic impacts of glaucoma as a leading cause of blindness, there is a pressing need for new innovative treatment strategies. Here we focus on the role of neuroinflammation in glaucoma and the opportunities that new findings in this area have for the development of future therapeutics.

Parkinson’s disease (PD) was first discovered 200 years ago. The current gold standard of clinical treatment is still mainly levodopa replacement therapy. Traditional Chinese medicine is the foundation of traditional medicine in China. Chinese herbs and acupuncture both exhibit remarkable efficacy in the treatment of PD. Clinical studies on the treatment of PD using Chinese herbs have confirmed that the combined use of Chinese herbs and the levodopa formulation can significantly increase the treatment effect and reduce toxic side effects. Basic studies further confirmed that various Chinese herbs and their monomeric substances can protect dopaminergic neurons in PD models. The major mechanisms include anti-inflammation, anti-oxidant, anti-apoptosis, neuroprotection, mitochondrial function protection, and regulation of gut microbiota. The function of acupuncture in the treatment of PD has also gradually received extensive attention in China and other countries. Acupuncture not only has peculiar advantages in the improvement of symptoms of PD patients, but also can attenuate adverse drug reactions, delay disease progression, and increase the quality of life of patients. Basic studies further confirmed that acupuncture can improve many motor symptoms in animal models of PD and has cumulative effects and follow-up effects. The major mechanisms include dopaminergic neuron protection functions, anti-inflammation and anti-oxidant effects, and the regulation of related neurotransmitters and neural circuits. The clinical application of acupuncture and Chinese herbs still requires strict randomized, double-blind, controlled design, multi-centre and large-sample sizeevidence-based clinical studies and follow-up observations of long-term efficacy to support the effect. In addition, the multi-target and multi-pathway therapeutic mechanisms need further studies.

Synaptotagmins(Syts) are a large family of integral membrane proteins that regulate synaptic function and membrane trafficking. Emerging evidences show involvement of Syts in human diseases. Here, we review the recent studies of several Syts (Syt1, 2, 7, 11, and 14) in the pathophysiological mechanisms of neurodegeneration disorders such as Alzheimer’s disease, Parkinson’s disease, and attention-deficit/hyperactivity disorder etc. A better understanding of the diverse physiological and pathological functions of different Syt isoforms is needed for potential therapeutic interventions in the future.

In contrast to neurons, the role of astrocytes has been matter of debate since their discovery, and mostly because of misconceptions about their role. As a consequence, technologies to study brain physiology have been designed around neurons, to answer one specific question, leaving glia experts with the only possibility to “hack” these techniques to describe astrocytes. As questions to answer about astrocytic functioning are based on factual observations, conclusions are often vague and cryptic, no matter how technically sound the work is. For instance, compelling evidence on calcium elevations has been provided, their dynamics have been studied in detail, but their role is still open for interpretation. Another astrocytic feature that carries a lot of mysteries is their complex morphology. The use of three-dimensional electron microscopy (3DEM) would most certainly be the best approach to unveil hidden features of such complex cells, nevertheless so far 3DEM hasn’t been fully exploited in that sense, nor techniques has been adapted for astrocytic observations in particular. One of the most ambitious neuroscience projects, the connectome, is pushing to their limits electron microscopy, image segmentation and 3D reconstruction and analysis, making it a very good candidate to adapt pipelines and methodologies to the study of astrocytic morphology. Here, we briefly review our current knowledge and technical state of art on 3D glia morphology, and speculate about its future directions.

In the past decade, the rapid development of viral tracing techniques, more precisely the neurotropic viral based mono-transsynaptic tracing strategy, provides a powerful tool to map synaptic connectivity in the central and peripheral nervous systems. This mini review provides a brief description of the principles of this tracing method, describe different strategies to trace the neural circuit from defined neuronal populations, and present an update of newly developed viral variants optimizing the method.