Publications by authors named "Nakai J"

To test the hypothesis that a sleep-like quiescent state enhances memory consolidation in the pond snail , we interposed a period in which snails experienced either a quiescent, sleeping state or an active, non-sleeping state following escape behavior suppression learning (EBSL). During EBSL training, the number of escapes made by a snail from a container was significantly suppressed using an external aversive stimulus (punishment). After training, the snails were divided into two groups.

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Heterozygous de novo mutations in Munc18-1, which is essential for neurotransmitter release, cause early infantile epileptic encephalopathy. Munc18-1-linked epilepsy is currently an untreatable disorder and its precise disease mechanism remains elusive. Here, we investigated how Munc18-1 pathogenic variants affect inhibitory neurons using .

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Article Synopsis
  • VPS45 is crucial for SNARE-mediated membrane fusion in endosomal trafficking, but its specific function is still unclear.
  • A genetic suppressor screen revealed that a mutation in another SM protein, VPS33A, can counteract the negative effects of losing VPS45, specifically a temperature-sensitive lethality.
  • The mutation (M376I) in VPS33A targets domain 3a, which is important for assembling SNARE complexes, emphasizing its significance in the function of endosomal SM proteins and membrane fusion processes.
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In the gastropod mollusk , insulin-like peptides in the central nervous system (CNS) control behavioral changes associated with associative learning. Insulin administration to the CNS enhances the synaptic plasticity involved in this type of learning, but it has remained unclear which molecules in the insulin response cascade are involved. Here, to advance a comprehensive analysis, we used two-dimensional electrophoresis and comparative quantitative mass spectrometry to perform a protein analysis investigating the CNS molecules that respond to insulin administration.

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PC12 cells, which are derived from rat adrenal pheochromocytoma cells, are widely used for the study of neuronal differentiation. NGF induces neuronal differentiation in PC12 cells by activating intracellular pathways via the TrkA receptor, which results in elongated neurites and neuron-like characteristics. Moreover, the differentiation requires both the ERK1/2 and p38 MAPK pathways.

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VPS45, one of the essential membrane trafficking factors, has been identified as a cause of severe congenital neutropenia 5 (SCN5), but its pathophysiological role remains unknown. Here, we developed a humanized model for three pathogenic VPS45 variants. We found that wild-type human VPS45 functionally complemented the loss of VPS-45 , and the pathogenic human VPS45 variants functioned almost normally with respect to larval development and endocytosis in .

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Article Synopsis
  • Exon-skipping therapy is a potential treatment for Duchenne muscular dystrophy (DMD) by targeting specific exons in the dystrophin gene, particularly focusing on a mild variant known as Δ3-9.
  • A study compared human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with either the Δ3-9 deletion, a frameshifting deletion (Δ3-7), or intact dystrophin, revealing that the Δ3-9 variant mimicked the expression patterns and electrical properties of healthy heart cells.
  • Antisense oligonucleotides targeting exon 8 successfully restored functional dystrophin and improved cell characteristics in the Δ3-7 cells, suggesting that modifying
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In the pond snail , serotonin (5-HT) plays an important role in feeding behavior and its associated learning (e.g., conditioned taste aversion: CTA).

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The pond snail is capable of learning by both classical conditioning and operant conditioning. Although operant conditioning related to escape behavior with punishment has been examined by some research groups, the molecular mechanisms are not known. In the present study, we examined changes in the expression levels of cAMP-response element binding protein 1 (CREB1), CREB2, CREB-binding protein (CBP), and monoamine oxidase (MAO) in the central nervous system (CNS) using real-time PCR following operant conditioning of escape behavior.

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Food deprivation activates forkhead box O (FOXO), a transcription factor downstream of insulin receptors. In the pond snail , insulin signaling and food deprivation improve memory consolidation following conditioned taste aversion (CTA) learning. We investigated the subcellular localization of FOXO in and changes in its expression levels following food deprivation, CTA learning, and insulin administration.

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Functional connectivity (FC) can provide insight into cortical circuit dysfunction in neuropsychiatric disorders. However, dynamic changes in FC related to locomotion with sensory feedback remain to be elucidated. To investigate FC dynamics in locomoting mice, we develop mesoscopic Ca imaging with a virtual reality (VR) environment.

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Adiponectin enhances insulin sensitivity, which improves cognition in mammals. How adiponectin affects the mechanism's underlying cognition, however, remains unknown. We hypothesized that experiments using the pond snail , which has long been used in learning and memory studies and in which the function of insulin-like peptides affect learning and memory, could clarify the basic mechanisms by which adiponectin affects cognition.

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This study evaluated the mechanism of temperature-controlled repeated thermal stimulation (TRTS)-mediated neuronal differentiation. We assessed the effect of SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, on neuronal differentiation of rat PC12-P1F1 cells, which can differentiate into neuron-like cells by exposure to TRTS or neurotrophic factors, including bone morphogenetic protein (BMP) 4. We evaluated neuritogenesis by incubating the cells under conditions of TRTS and/or SP600125.

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Here we describe the microglia-targeting adeno-associated viral (AAV) vectors containing a 1.7-kb putative promoter region of microglia/macrophage-specific ionized calcium-binding adaptor molecule 1 (Iba1), along with repeated miRNA target sites for microRNA (miR)-9 and miR-129-2-3p. The 1.

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Insulin and insulin-like peptides (ILP) help to maintain glucose homeostasis, whereas insulin-like growth factor (IGF) promotes the growth and differentiation of cells in both vertebrates and invertebrates. It is sometimes difficult to distinguish between ILP and IGF in invertebrates, however, because in some cases ILP has the same function as IGF. In the present review, therefore, we refer to these peptides as ILP/IGF signaling (IIS) in invertebrates, and discuss the role of IIS in memory formation after classical conditioning in invertebrates.

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Myoepithelial cells (MECs) are responsible for receiving stimuli from the central nervous system and translating their responses into the form of secretion into glandular tissue, including salivary glands (SG), sweet glands, and mammary glands. SG MECs cause the secretion of serous saliva by contracting of acini/ductal cells with acetylcholine (Ach) from parasympathetic nerves via muscarinic receptors. To response the parasympathetic physiological stimulation, SG epithelial cell-derived MECs are supposed to be induced and placed adjacent to parasympathetic system nerve ends in SGs by forming a neuro-myoepithelial junction.

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The Gly16Arg polymorphism results in a G to C nucleotide mutation in the human beta 2-adrenergic receptor (ADRB2) gene and has a relationship with obesity; however, this substitution’s effects on food preferences are unclear. Therefore, we determined this relationship among healthy young adults (mean age, 23.4; n = 52).

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The rapid progress of calcium imaging techniques has reached a point where the activity of thousands to tens of thousands of cells can be recorded simultaneously with single-cell resolution in a field-of-view (FOV) of about ten mm. Consequently, there is a pressing need for developing automatic cell detection methods for large-scale image data. Several research groups have proposed automatic cell detection algorithms.

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Nutritional status affects cognitive function in many types of organisms. In the pond snail , 1 day of food deprivation enhances taste aversion learning ability by decreasing the serotonin (5-hydroxytryptamin; 5-HT) content in the central nervous system (CNS). On the other hand, after 5 days of food deprivation, learning ability and the CNS 5-HT concentration return to basal levels.

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Impairment of episodic memory, a class of memory for spatiotemporal context of an event, is an early symptom of Alzheimer's disease. Both spatial and temporal information are encoded and represented in the hippocampal neurons, but how these representations are impaired under amyloid β (Aβ) pathology remains elusive. We performed chronic imaging of the hippocampus in awake male amyloid precursor protein () knock-in mice behaving in a virtual reality environment to simultaneously monitor spatiotemporal representations and the progression of Aβ depositions.

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Fast and wide field-of-view imaging with single-cell resolution, high signal-to-noise ratio, and no optical aberrations have the potential to inspire new avenues of investigations in biology. However, such imaging is challenging because of the inevitable tradeoffs among these parameters. Here, we overcome these tradeoffs by combining a resonant scanning system, a large objective with low magnification and high numerical aperture, and highly sensitive large-aperture photodetectors.

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An adult female sika deer (Cervus nippon aplodontus) inhabiting Nara Park, Nara, Japan, had broken bone injuries from a car accident. During its treatment, we found that the sika deer had severe anemia and the fracture remained unhealed throughout. Peripheral blood smear revealed piroplasms in the erythrocytes, which were identified as merozoites of undescribed Theileria species, widely found in sika deer in Japan.

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GABAergic interneurons play a critical role in tuning neural networks in the central nervous system, and their defects are associated with neuropsychiatric disorders. Currently, the mDlx enhancer is solely used for adeno-associated virus (AAV) vector-mediated transgene delivery into cortical interneurons. Here, we developed a new inhibitory neuron-specific promoter (designated as the mGAD65 promoter), with a length of 2.

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In the hippocampus, spatial and nonspatial information are jointly represented as a neural map in which locations associated with salient features are over-represented by increased densities of relevant place cells. Although we recently demonstrated that experience-dependent establishment of these disproportionate maps is governed by selective stabilization of salient place cells following their conversion from non-place cells, the underlying mechanism for pre-established map reorganization remained to be understood. To this end, we investigated the changes in CA1 functional cellular maps imaged using two-photon calcium imaging in mice performing a reward-rearrangement task in virtual reality.

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