MARCKS Phosphorylation at Ser46 reflects neurite degeneration and is a candidate marker for presymptomatic and preaggretaion pathology of Alzheimer’s disease. Here, we demonstrate the similar change in Parkinson’s disease and Dementia with Lewy body prior to alpha-synuclein aggregation, and suggest an ultra-early stage pathology shared by different groups of neurodegenerative diseases.
Kyota Fujita, Hidenori Homma, Kanoh Kondo, Masashi Ikuno, Hodaka Yamakado, Kazuhiko Tagawa, Shigeo Murayama, Ryosuke Takahashi and Hitoshi Okazawa
eNeuro 16 August 2018, ENEURO.0217-18.2018; DOI: https://doi.org/10.1523/ENEURO.0217-18.2018
The ventral tegmental area (VTA) and substantia nigra (SN) are involved in dopaminergic brain functions. Given that there are no VTA or SN anatomical MRI templates for Asian people, we created these templates and showed suitability for Asian brains using anatomical and resting state functional MRI data.
The research team led by Profs. Norio Ozaki (Nagoya University) and Hideyuki Okano (Keio University) revealed that a rare RELN variant, initially identified in a schizophrenic patient, causes a loss of directional stability during neuronal migration using human iPSCs generated from the patient. These findings are expected to contribute to understanding the molecular pathophysiology and/or developing drugs for mental disorders.
Arioka Y, Shishido E, Kubo H, Kushima I, Yoshimi A, Kimura H, Ishizuka K, Aleksic B, Maeda T, Ishikawa M, Kuzumaki N, Okano H, Mori D, Ozaki N: Single-cell trajectory analysis of human homogenous neurons carrying a rare RELN variant. Transl Psychiatry 8 (1):129, 2018
Intellectual deterioration may play a key role in work disturbances in patients with schizophrenia. The study demonstrated probabilistic models to estimate work status in patients with schizophrenia based on relevant factors including intellectual deterioration. Feedback on work status would support social rehabilitation in patients with schizophrenia.
The present study demonstrated that tau pathology in orbitofrontal cortex (OFC) may provoke focal neurotoxicity in OFC and the following disruption of the OFC-uncinate fasciculus network, leading to the emergence and progression of apathy in Alzheimer’s disease. The current data also raise the possibility that emerging antitau drugs would be efficacious for suppressing apathy.
By combining an 8K ultra-high-definition camera with spinning-disk one-photon confocal microscopy, we succeeded in imaging of activity of presynaptic axonal boutons of neurons projecting to the motor cortex in a behaving mouse. We detected axonal boutons with highly correlated activity over the 1 mm2 field.
This article was published in "Biochemical and Biophysical Research Communications, Volume 500, Issue 2".
Brain damage such as stroke is a devastating neurological condition, which may severely compromise patient quality of life. No effective medication-mediated intervention to accelerate rehabilitation has been established. We found that a small compound, edonerpic-maleate, facilitated experience-driven synaptic glutamate AMPAreceptor delivery and resulted in the acceleration of motor function recovery after brain damage in a training-dependent manner.
Bioluminescence is a natural light source based on luciferase catalysis of its substrate luciferin. We performed directed evolution on firefly luciferase using a red-shifted and highly deliverable luciferin analog to establish AkaBLI, an all-engineered bioluminescence in vivo imaging system.
This research result was published in "Science 23 Feb 2018".
Mutations in the progranulin (PGRN) gene cause a tau pathology-negative and TDP43 pathology-positive form of frontotemporal lobar degeneration (FTLD-TDP). We generated a knock-in mouse harboring the R504X mutation (PGRN-KI).
This research result was published on Nature Communications, 30 January 2018.
Subcortical regions have a pivotal role in cognitive, affective, and social functions in humans, and the structural and functional abnormalities of the regions have been associated with various psychiatric disorders.
This research result was published on Scientific Reports, volume 8, 19 January 2018.
We examined the neural basis of persuasion-induced changes in attitude toward and away from norms using fMRI. We measured brain activity while human participants were exposed to persuasive messages directed toward specific norms.
This research result was published on Scientific Reports volume 7, Article number: 16295, 24 November 2017.
Researchers at the RIKEN Brain Science Institute and collaborative project have discovered that the benefits of stimulating the brain with direct current come from its effects on astrocytes — not neurons — in the mouse brain. Published in Nature Communications, the work shows that applying direct current to the head releases synchronized waves of calcium from astrocytes that can reduce depressive symptoms and lead to a general increase in neural plasticity — the ability of neuronal connections to change when we try to learn or form memories.
In cerebellar Purkinje cells (PCs), dendritic territories by climbing and parallel fiber (PF) innervations are segregated. Here, we show that the segregation of territories occurs as a result of elimination of PF synapses from the proximal dendrites, and that PF synapse elimination is controlled by the type 1 metabotropic glutamate receptor to protein kinase Cg signaling pathway in PCs.
Press Release Mirror Neurons in a New World Monkey, Common Marmoset
The research team including researchers from NCNP and RIKEN BSI found neurons in the ventrolateral frontal cortex with characteristic “mirror” properties quite similar to those in macaques. This finding suggests that mirror neurons occur in a common ancestor of New and Old World monkeys and its common properties are preserved during the course of primate evolution.
Researchers at the RIKEN Brain Science Institute in Japan have developed a new system for imaging the activity of individual neurons in the marmoset brain. Published in Cell Reports, the study shows how amplifying genetically encoded fluorescent signals with TET-inducible gene expression allows hundreds of individual neurons in the primate brain to be imaged simultaneously over a period of several months.
It remains unclear how readiness for Ca2+ -dependent exocytosis depends on varying degrees of SNARE complex assembly. We demonstrated the SNARE assembly using ﬂuorescence lifetime imaging (FLIM) of Forster resonance energy transfer (FRET) between three pairs of neuronal SNAREs in presynaptic boutons and pancreatic beta cells in the islets of Langerhans.
The research team including researchers from RIKEN BSI and NIPS established a new method to visualize dendritic spines in the living marmoset brain. The method that utilizes two-photon microscopy in combination with virus vectors to enhance the expression of fluorescent signals makes it possible to study neural circuits in primate brains.
Press Release Real x-ray vision: see-through brains ready for study
Researchers at the RIKEN Brain Science Institute in Japan have developed a new technique for creating transparent tissue that can be used to illuminate 3D brain anatomy at very high resolutions. Published in Nature Neuroscience, the work showcases the new technology and its practical importance in clinical science by showing how it has given new insights into Alzheimer’s disease plaques.
The research team led by Prof. Okazawa (Tokyo Medical and Dental University) developed a new technique for observation
of autophagy in the brain in vivo, and revealed unexpected roles of autophagy in Alzheimer's disease
including the increase of intracellular Amyloid beta by starvation and circadian rhythm of neuronal autophagy activity.
Brains, Genes, and Primates
Brain/MINDS: brain-mapping project in Japan- Philosophical Transactions B
Hideyuki Okano, Atsushi Miyawaki, Kiyoto Kasai