We are living in the golden age of neuroscience. Spurred on by technological advances in areas as diverse as imaging, genetics, big data, and artificial intelligence. The field of neuroscience is advancing at its fastest pace ever. Individuals with many different skills and backgrounds are pouring into our field and attempting to answer the profound questions about how our brain functions in health and disease.
While we can be justly proud of the advances techniques such as optogenetics, multi-electrode recordings, and new types of brain imaging have brought to our understanding of the brain, the challenge of translating the discoveries that are made at the fundamental neuroscience level to the benefit of society and to patients who suffer from brain diseases continues. There are over one thousand diseases that affect the brain, and the sad truth is that for most of them we still have no effective treatment. Understanding brain function is valuable and important, but to really make a difference to society, we must be able to translate these new understandings to the direct benefit of patients and society. This is the purpose of the Journal of Translational Neuroscience. In this inaugural issue, we begin the long journey of facilitating the publication of world class papers that presage a world in which advances in understanding of brain function can lead to new diagnostics and treatments for brain diseases.
The Journal of Translational Neuroscience is a child of the International Association of Translational Neuroscience（IATN）. This organization was founded in 2012 by a group of leading scientists and physicians in China, and is headquartered at the Beijing Institute for Brain Disorders（BIBD）. Since inception, it has since grown to encompass about a dozen leading neuroscience centres worldwide. The shared vision of this group includes a commitment to develop new understandings, diagnostics, and treatments around diseases that affect the human brain. Some of the key subjects of inquiry include topics such as neurodegenerative disorders, stroke, brain tumor, mental illness, as well as developmental brain disorders. The journal will accept high quality publications in all of these areas, as well as papers which illuminate technological advances relevant to translational neuroscience.
The last few decades have taken the field of neuroscience from one with great promise to our current status characterized by a huge increase in our understanding of mechanisms of brain function. Now it is time for us to turn these advances and understanding into tangible benefits for patients.
Welcome to the Journal of Translational Neuroscience.

Editors-in-Chief：
Xiaomin Wang and Max S Cynader

No less than 17 Nobel Prizes have been awarded the area of neurosocience and no less than 40 laureates. The first prize was given to Camillo Golgi and Ramón y Cajal in 1906 and the last one so far, to John O’Keefe and May-Britt and Edvard I. Moser in 2014.
This presentation of the laureates will not follow the time sequence of the prizes. Instead, I have grouped them in different categories.

Protein phosphorylation is an important posttranslational modification of group I metabotropic glutamate receptors (mGluR1 and mGluR5 subtypes, mGluR1/5) which are widely distributed throughout the mammalian brain. Several common protein kinases are involved in this type of modification, including protein kinase A, protein kinase C, and extracellular signal-regulated kinase. Through constitutive and activity-dependent phosphorylation of mGluR1/5 at specific residues, protein kinases regulate trafficking, subcellular/subsynaptic distribution, and function of modified receptors. Increasing evidence demonstrates that mGluR1/5 phosphorylation in the mesolimbic reward circuitry is sensitive to chronic psychostimulant exposure and undergoes adaptive changes in its abundance and activity. These changes contribute to long-term excitatory synaptic plasticity related to the addictive property of drugs of abuse. The rapid progress in uncovering the neurochemical basis of addiction has fostered bench-to-bed translational research by targeting mGluR1/5 for developing effective pharmacotherapies for treating addiction in humans. This review summarizes recent data from the studies analyzing mGluR1/5 phosphorylation. Phosphorylation-dependent mechanisms in stimulant-induced mGluR1/5 and behavioral plasticity are also discussed in association with increasing interest in mGluR1/5 in translational medicine.

China has made significant progress in modernizing its healthcare system in the past 20 years. However, there are some issues that are difficult to solve on the current healthcare status, including the lack of medical care satisfaction in rural areas and urban areas, excessive consumption of medical resources, conflict and tension between the healthcare provider and patients, and the problems caused by the change of model of healthcare. Therefore, the State Council introduced the Opinions of the CPC Central Committee and the State Council on Deepening the Health Care System Reform in 2009 in order to provide basic, safe, effective, convenient and affordable healthcare for all residents. Despite the goals and policies set by the government, how to implement them remains to be challenging. Like evidence-based medicine, comparative effective research (CER) which started in the US in 2000's can provide diagnosis and treatment information for patients, doctors, and health policy makers to make decisions on the effective ways of caring for both individual and population. It also may apply to the conditions of healthcare reform in China. And there are opportunities and challenges of conducting CER in our country. We suggest that the government should establish the national-level CER research institute, CER Leadership Committee and relevant standards, fund the CER projects, and begin CER in certain disciplines.

Rasmussen's encephalitis (RE), which was first described by Rasmussen in 1958, is a rare, dispersed, and progressive neurological syndrome that is characterized by focal epilepsy, unilateral inflammation of the cerebral cortex, progressive hemiplegia and cognitive deterioration. The etiology of this syndrome remains under investigation, and it is hypothesized and widely accepted that RE is a T-cell-mediated autoimmune response. However, the antigenic epitopes and mechanisms are still unknown. The pathological characteristics of RE are cortical inflammation, neuronal loss, and gliosis that are confined to one cerebral hemisphere. Hemispherectomy remains the only cure for the seizures and cognitive deterioration associated with the disease, but this procedure results in inevitable functional loss in the brain. Compared with surgery, immunomodulatory treatments are expected to cause less neurological deficits, but with limited clinical effect.

Neurogenic bladder (NB) dysfunction caused by spinal cord injury (SCI) or diseases of the central nervous system or peripheral nerves is a major medical and social problem. Traditional treatments to NB include medication, injection of Botulinum toxin A into the detrusor, neuromodulation and surgery. There are also emerging approaches, such as tissue engineering, stem cell transplantation and gene therapy. In recent years, we have carried out explorations in both therapeutic areas and tried to translate basic research into clinical practice. This paper reviews our work in this regard, and provides references for future research.

Clinical observation shows that men and women are different in prevalence, symptoms, and responses to treatment of several psychiatric disorders, including schizophrenia. While the etiology of gender differences in schizophrenia is only partially understood, recent genetic studies suggest significant sex-specific pathways in the schizophrenia between men and women. More research is needed to understand the causal roles of sex differences in schizophrenia in order to ultimately develop sex-specific treatment of this serious mental illness. In the present review, we will outline the current evidence on the sex-related factors interaction with disease onset, symptoms and treatment of schizophrenia, and discuss the potential molecular mechanisms that may mediate their cooperative actions in schizophrenia pathogenesis.

Objective: Although lithium has been a commonly prescribed neurotrophic/neuroprotective mood-stabilizing agents, its effect on spontaneous brain activity in patients with bipolar depression remains unclear. The aim of this study is to reveal the basic mechanism underlying the pathological influences of lithium on resting-state brain function of bipolar depression patients. Methods: 97 subjects including 9 bipolar depression patients with lithium treatment, 19 bipolar depression patients without lithium treatment and 69 healthy controls, were recruited to participate in this study. Amplitude of low-frequency fluctuation (ALFF) and fractional amplitude of low-frequency fluctuation (fALFF) were used to capture the changes of spontaneous brain activity among different groups. In addition, further analysis in terms of Hamilton Depression Rating Scale, the number of depressive episodes, and illness duration in pooled bipolar depression patients were conducted, which combined FLEF and fALEF to identify the basic neural features of bipolar depression patients. Results: It was observed from the imaging results that both the bipolar depression patients receiving lithium treatment and healthy control subjects showed significantly decreased ALFF/fALFF values in the right anterior cingulate cortex and right middle frontal gyrus compared to that from the bipolar depression patients without lithium treatmetn. The ALFF values of the right middle temporal gyrus was also found to be negative related to the number of depressive episode and the total episodes. Conclusions: Our findings suggested that the bipolar depression subjects were identified to have abnormal ALFF/ fALFF in the cortico-limbic systems, including regions like right anterior cingulate cortex, bilateral middle frontal gyrus, right orbital frontal gyrus, and right middle temporal gyrus. In addition, it was also revealed that the decreased ALFF/fALFF in the right anterior cingulate cortex and right middle frontal gyrus might be a biomarker that is related to the lithium effects.

The International Alliance for Translational Neuroscience (IATN) is an international multi-institutional organization aimed at achieving decisive advancements in the field of neuroscience and associated disorders by utilizing existing strengths of each institution to promote integration of research, education/training and collaboration of translational neuroscience research activities among the member institutions.

Over the past few decades, the field of neuroscience has grown dramatically and made tremendous progress. From its origins in physics, philosophy and psychology, the field has grown to include among its practitioners talented individuals not only from these founding disciplines but from many others. Though our progress in Neuroscience has been immense, there is still much to be done, and it has become clear that a large number of overlapping complimentary skill sets are required to make progress on the challenging problems that lie ahead. The vision of an interdisciplinary, integrated neuroscience enterprise has characterized our University since the inception of the field. The University of British Columbia is one of the world’s top leading academic institutions, and its Faculty of Medicine is renowned for its broad expertise in research, teaching, and clinical innovation. From the very beginning of the foundation of the University, UBC’s commitment to better understanding the brain was a priority. Just seven years before UBC opened its doors in 1913, the Nobel Prize was awarded to Ramon y Cajal and Camillo Golgi, the scientists who discovered neurons, the amazing, multi-variant, cells that communicate information to, from and within the brain. The study of the brain, was still in its infancy in 1906 when the Nobel Prize was awarded, but one of the first courses offered at UBC was Elementary Psychology, the study of brain and behaviour.

Karolinska Institutet is one of the founding members of the International Alliance for Translational Neuroscience, IATN. This alliance was established in Beijing in 2012 and it presently includes seven members worldwide. Karolinska Institutet has a long tradition in research on the nervous system. Early on it was mainly represented by the Department of Neurophysiology and the Nobel Laureate Ragnar Granit, and the Department of Physiology, where Ulf von Euler, also a Nobel Laureate, carried out pioneering work on catecholamines, substance P and prostaglandins (see Grant G: The Nobel Prizes in the Field of Neuroscience which was published in the same issue). Today two departments are specifically devoted to this field, the Department of Neuroscience and the Department of Clinical Neuroscience. In addition, this field of research is explored at the Departments of Physiology and Pharmacology, Cell and Molecular Biology, Medical Biochemistry and Biophysics, as well as at the Department of Neurobiology, Care Sciences and Society. All together neuroscience at Karolinska Institutet represents a very strong discipline.

Abstract Autism spectrum disorders (ASD) area group of neurodevelopmental disorders that affect up to 1.5% of population in the world. Recent largescale genomic studies show that genetic causes of ASD are very heterogeneous. Gene ontology, pathwayanalysis and animal model studies have revealed several potential converging mechanisms including postsynaptic dysfunction of excitatory synapses. In this review, we focus on the structural and functional specializations of dendritic spines, and describe their defects in ASD.We use Fragile X syndrome, Rett syndrome and Phelan-McDermid syndrome, three of the most studied neurodevelopmental disorders with autism features, as examples to demonstrate the significant contribution made by mouse models towards the understanding of monogenic ASD. We envision that the development and application of new technologies to study the function of dendritic spines in valid animal models will eventually lead to innovative treatments for ASD.

Abstract The quest to find novel therapeutics for mental and neurological disorders has been hindered by the lack of access to live human brain samples and relevant experimental models. Conventional 2D human pluripotent stem cell-derived neuronal cultures and animal models do not fully recapitulate many endogenous human biochemical processes and diseasephenotypes. Currently, the majority of candidate drugs obtained from preclinical testing in conventional systems does not usually translate into success and have a high failure rate in clinical trials. Recent advancements in bioengineering and stem cell technologies have resulted in three-dimensional brain-like tissues, such as oragnoids,which better resemble endogenous tissue and are more physiologically relevant than monolayer cultures. These brain-like tissues can bridge the gap between existing models and the patient, and may revolutionize the field of translational neuroscience. Here, we discuss utilities and challenges of using stem cell-derived human brain tissues in basic research and pharmacotherapy

Abstract Multiple sclerosis (MS) is characterized by neurological symptoms that are separated in time and space, which correlate with demyelination and white matter lesions. The conventional pathophysiological model is that an autoimmune reaction against the myelinated nerve sheath results in demyelination, accompanied by axon damage and the death of oligodendrocytes that produce myelin. There is no cure for MS, but current treatments are primarily aimed at suppressing the autoimmune reaction, with the goal of reducing demyelination. These treatments have limited efficacy and developing better treatments for MS remains an important goal. Here we argue that the autoimmune reaction may be secondary to neurodegeneration or neurotoxicity, and that protecting neurons from glutamate-mediated toxicity may be a better therapeutic strategy than targeting the immune system. We have recently demonstrated that a protein-protein interaction between the GluR2 subunit of the AMPA (α-Amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid) glutamate receptor and GAPDH (Glyceraldehyde 3-phosphate dehydrogenase) is elevated in human MS plaques and in an animal model of MS. Disrupting this interaction in a rodent model restores neurological function, preserves myelin, and protects neurons, oligodendrocytes and axons. The peptide we created to block the GluR2-GAPDH interaction also reduces immune system activation, suggesting that autoimmunity is not necessarily the primary etiology in MS. The GluR2-GAPDH interaction may promote cell death via increased calcium influx through non-GluR2-containing AMPA receptors, or through the p53 and Siah1 cell death pathways.

Neurological and psychiatric disorders collectively constitute the greatest burden of disease. However, the human brain is the most complex of biological systems and therefore accurately modeling brain disorders presents enormous challenges. A large range of therapeutic approaches across a diverse collection of brain disorders have been found to show great promise in preclinical testing and then failed during clinical trials. There are a variety of potential reasons for such failures, on both the preclinical and clinical sides of the equation. In this article, I will focus on the key issues of validity in animal models. I will discuss two forms of construct validity, ‘genetic construct validity’ and ‘environmental construct validity’, which model specific aspects of the genome and ‘envirome’ relevant to the disorder in question. The generation of new gene-edited animal models has been facilitated by new technologies, the most notable of which are CRISPR-Cas systems. These and other technologies can be used to enhance construct validity. Finally, I will discuss how face validity can be optimized, via more sophisticated cognitive, affective and motor behavioural tests, translational tools and the integration of molecular, cellular and systems data. Predictive validity cannot yet be assessed for the many preclinical models where we currently lack effective clinical interventions, however this will change as the translational pipeline is honed to deliver therapies for a range of devastating disorders.