Brain/MINDS: brain-mapping project in Japan Okano, Hideyuki; Miyawaki, Atsushi; Kasai, Kiyoto
Philosophical transactions - Royal Society. Biological sciences,
05/2015, Volume:
370, Issue:
1668
Journal Article
Peer reviewed
Open access
There is an emerging interest in brain-mapping projects in countries across the world, including the USA, Europe, Australia and China. In 2014, Japan started a brain-mapping project called Brain ...Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS). Brain/MINDS aims to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain, and takes advantage of a unique non-human primate animal model, the common marmoset (Callithrix jacchus). In Brain/MINDS, the RIKEN Brain Science Institute acts as a central institute. The objectives of Brain/MINDS can be categorized into the following three major subject areas: (i) structure and functional mapping of a non-human primate brain (the marmoset brain); (ii) development of innovative neurotechnologies for brain mapping; and (iii) human brain mapping; and clinical research. Brain/MINDS researchers are highly motivated to identify the neuronal circuits responsible for the phenotype of neurological and psychiatric disorders, and to understand the development of these devastating disorders through the integration of these three subject areas.
Abstract
Supercentenarians (those aged ≥110 years) are approaching the current human longevity limit by preventing or surviving major illness. Identifying specific biomarkers conducive to exceptional ...survival might provide insights into counter-regulatory mechanisms against aging-related disease. Here, we report associations between cardiovascular disease-related biomarkers and survival to the highest ages using a unique dataset of 1,427 oldest individuals from three longitudinal cohort studies, including 36 supercentenarians, 572 semi-supercentenarians (105–109 years), 288 centenarians (100–104 years), and 531 very old people (85–99 years). During follow-up, 1,000 participants (70.1%) died. Overall, N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6, cystatin C and cholinesterase are associated with all-cause mortality independent of traditional cardiovascular risk factors and plasma albumin. Of these, low NT-proBNP levels are statistically associated with a survival advantage to supercentenarian age. Only low albumin is associated with high mortality across age groups. These findings expand our knowledge on the biology of human longevity.
Summary The common marmoset ( Callithrix jacchus ), a small New World primate, has been attracting much attention in the research field of biomedical science and neuroscience, based on its (i) ...cross-reactivity with human cytokines or hormones, (ii) comparative ease in handling due to its small size, (iii) high reproductive efficiency, (iv) establishment of basic research tools, and (v) advantages of its unique behavioral and cognitive characters. Various neurological disease models have been developed in the common marmoset, including Parkinson's disease, Huntington's disease, Alzheimer's disease, stroke, multiple sclerosis and spinal cord injury. We recently developed transgenic common marmoset with germline transmission, which is expected to provide a new animal model for the study of human diseases. In this review, we summarize the recent progress of biomedical research and neuroscience using common marmoset as an excellent model system.
Astrocytes become reactive following various brain insults; however, the functions of reactive astrocytes are poorly understood. Here, we show that reactive astrocytes function as phagocytes after ...transient ischemic injury and appear in a limited spatiotemporal pattern. Following transient brain ischemia, phagocytic astrocytes are observed within the ischemic penumbra region during the later stage of ischemia. However, phagocytic microglia are mainly observed within the ischemic core region during the earlier stage of ischemia. Phagocytic astrocytes upregulate ABCA1 and its pathway molecules, MEGF10 and GULP1, which are required for phagocytosis, and upregulation of ABCA1 alone is sufficient for enhancement of phagocytosis in vitro. Disrupting ABCA1 in reactive astrocytes result in fewer phagocytic inclusions after ischemia. Together, these findings suggest that astrocytes are transformed into a phagocytic phenotype as a result of increase in ABCA1 and its pathway molecules and contribute to remodeling of damaged tissues and penumbra networks.Astrocytic phagocytosis has been shown to play a role in synaptic pruning during development, but whether adult astrocytes possess phagocytic ability is unclear. Here the authors show that following brain ischemia, reactive astrocytes become phagocytic and engulf debris via the ABCA1 pathway.
Brain/MINDS (Brain Mapping by Integrated Neurotechnologies for Disease Studies) is a national brain project started by Japan in 2014. With the goal of developing the common marmoset as a model animal ...for neuroscience, the project aims to build a multiscale marmoset brain map, develop new technologies for experimentalists, create transgenic lines for brain disease modeling, and integrate translational findings from the clinical biomarker landscape. Brain/MINDS will collaborate with global brain projects to share technologies and resources.
The Japanese national brain initiative called Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) initiative was launched in 2014 with a focus on the common marmoset as a model system.
Hearing loss due to damage to auditory hair cells is normally irreversible because mammalian hair cells do not regenerate. Here, we show that new hair cells can be induced and can cause partial ...recovery of hearing in ears damaged by noise trauma, when Notch signaling is inhibited by a γ-secretase inhibitor selected for potency in stimulating hair cell differentiation from inner ear stem cells in vitro. Hair cell generation resulted from an increase in the level of bHLH transcription factor Atoh1 in response to inhibition of Notch signaling. In vivo prospective labeling of Sox2-expressing cells with a Cre-lox system unambiguously demonstrated that hair cell generation resulted from transdifferentiation of supporting cells. Manipulating cell fate of cochlear sensory cells in vivo by pharmacological inhibition of Notch signaling is thus a potential therapeutic approach to the treatment of deafness.
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► Sensory hair cell regeneration is demonstrated in an adult mammal ► Inhibition of Notch stimulates hair cell regeneration after acoustic trauma ► Hair cells are derived from transdifferentiation of cochlear supporting cells ► Frequency region of hearing recovery corresponds to area of hair cell replacement
Deafness caused by loss of hair cells, the receptor cells for sound, is not reversible. Mizutari et al. induce hair cell regeneration leading to recovery of hearing in mice by treatment with a drug-inhibiting Notch signaling.
Amyotrophic lateral sclerosis (ALS) is a representative neurological disease that is known to devastate entire motor neurons within a period of just a few years. Discoveries of the specific ...pathologies of relevant RNA-binding proteins, including TAR DNA-binding protein-43 (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS), and the causative genes of both familial and sporadic ALS have provided crucial information that could lead to a cure. In recent ALS research the GGGGCC-repeat expansion in the C9orf72 gene was identified as one of the most important pathological findings, suggesting the significance of both nuclear dysfunction due to dipeptide repeat proteins (DPRs) and RNA toxicity (such as pathological alterations of non-coding RNAs). In research on model animals carrying ALS-related molecules, the determination of whether a factor is protective or toxic has been controversial. Herein, we review the findings regarding NEAT1 RNA and C9orf72 GGGGCC repeats associated with ALS, from the viewpoint of conversion from the protective stage in the nucleus in early-phase ALS to late-phase induction of cell death. This review will provide insights for the development of RNA effectors as novel ALS treatments.
•The pathological mechanism of ALS is one of the 'nucleopathies'.•The repeat expansion in the C9orf72 gene is also important for ALS pathogenesis.•NEAT1_2 lncRNA has an important role in forming a paraspeckle structure.•NEAT1_2 lncRNA and NEAT1_1 RNA could determine the fate of the motor neuron in ALS.
The enthusiasm for producing patient-specific human embryonic stem cells using somatic nuclear transfer has somewhat abated in recent years because of ethical, technical, and political concerns. ...However, the interest in generating induced pluripotent stem cells (iPSCs), in which pluripotency can be obtained by transcription factor transduction of various somatic cells, has rapidly increased. Human iPSCs are anticipated to open enormous opportunities in the biomedical sciences in terms of cell therapies for regenerative medicine and stem cell modeling of human disease. On the other hand, recent reports have emphasized the pitfalls of iPSC technology, including the potential for genetic and epigenetic abnormalities, tumorigenicity, and immunogenicity of transplanted cells. These constitute serious safety-related concerns for iPSC-based cell therapy. However, preclinical data supporting the safety and efficacy of iPSCs are also accumulating. In this Review, recent achievements and future tasks for safe iPSC-based cell therapy are summarized, using regenerative medicine for repair strategies in the damaged central nervous system (CNS) as a model. Insights on safety and preclinical use of iPSCs in cardiovascular repair model are also discussed.
Pluripotent stem cells (PSCs) can differentiate into all cell types in the body, and their differentiation procedures recapitulate the developmental processes of embryogenesis. Focusing on ...neurodevelopment, we describe here the application of knowledge gained from embryology to the neural induction of PSCs. Furthermore, PSC‐based neural modeling provides novel insights into neurodevelopmental processes. In particular, human PSC cultures are a powerful tool for the study of human‐specific neurodevelopmental processes and could even enable the elucidation of the mechanisms of human brain evolution. We also discuss challenges and potential future directions in further improving PSC‐based neural modeling.
In this review, we focus on pluripotent stem cell (PSC)‐based models for neural specification in early embryogenesis, patterning of the nervous system, and human‐specific neurodevelopmental process and discuss recent studies, remaining issues, and future strategies.
For the past few decades, spinal cord injury (SCI) has been believed to be an incurable traumatic condition, but with recent developments in stem cell biology, the field of regenerative medicine has ...gained hopeful momentum in the development of a treatment for this challenging pathology. Among the treatment candidates, transplantation of neural precursor cells has gained remarkable attention as a reasonable therapeutic intervention to replace the damaged central nervous system cells and promote functional recovery. Here, we highlight transplantation therapy techniques using induced pluripotent stem cells to treat SCI and review the recent research giving consideration to future clinical applications.
•Transplantation of iPSC-derived neural precursor cells (NPCs) shows beneficial effects for spinal cord injury (SCI).•Because unsafe iPSC-NPC lines can form tumors after grafting, provisions to attenuate this risk are substantially important.•Clinical application for SCI patients using iPSCs will be conducted in the near future.
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