Biology subjects

Uemura, N.

Publications and source records attributed to Uemura, N..

5 recordsLinked to original sources

bioRxiv2025

Forgetting in Drosophila consists of an increase in uncertainty rather than a stochastic loss of memory

While forgetting has been studied extensively in various organisms, its precise nature has often been unclear. Here, we used behavioral experiments in Drosophila to determine that a significant aspect of forgetting consists of a decrease in the ability of a memory to induce an appropriate behavior. We tested flies for memory retention at various times after training and then separately retested both flies that chose correctly and those that chose incorrectly. Although the ability to choose correctly decreased over time, we could not measure any differences in memory between flies that initially chose correctly and those that chose incorrectly upon retest. This suggests that forgetting is unlikely to consist of a spontaneous loss of a memory but instead consists of a decrease in the probability of flies that remember choosing the correct behavioral response. Thus, although flies maintain memory over time, there is an increase in uncertainty associated with this memory. We find that forgetting of long-term memories and accelerated forgetting in old flies occur in a similar manner.

neuroscience↗

bioRxiv2024

Lysophosphatidic acid receptor 1 influences disease severity in a mouse model of multiple sclerosis

Multiple sclerosis (MS), a chronic inflammatory disease affecting the central nervous system (CNS), is characterized by demyelination and axonal degeneration. Current treatments, which focus mainly on reducing lymphocyte infiltration into the CNS, are insufficient due to serious side effects and limited effectiveness; thus, identifying drugs with new mechanisms of action is crucial. Lysophosphatidic acid (LPA), a bioactive lipid produced by the enzyme autotaxin, may play a role in MS pathogenesis. Specifically, the LPA1 subtype of LPA receptors is linked to release of inflammatory cytokines in the CNS, and to demyelination in the peripheral nervous system. Our study investigated the role of LPA1 in a mouse model of MS. Knocking out the LPA1 gene in mice with experimental autoimmune encephalomyelitis improved clinical outcomes and reduced demyelination. Additionally, the absence of LPA1 reduced activation of Iba1-positive cells. Treatment with AM095, an LPA1 antagonist, tended to improve clinical outcomes and reduce levels of inflammatory mediators. These findings indicate that activation of LPA1 contributes to MS pathogenesis by promoting microglial activation and infiltration of peripheral immune cells.

neuroscience↗

bioRxiv2024

Oligodendrocyte precursor cells exacerbate acute CNS inflammation via macrophage and T cell activation in a mouse model of multiple sclerosis

Oligodendrocyte precursor cells (OPCs) are a type of glial cell that differentiates into mature oligodendrocytes, a cell type that contributes to myelination, but their roles in the pathologies are not fully understood. Activities other than differentiation into oligodendrocytes have recently been reported for OPCs present in the inflammatory milieu, but intervention studies using animal models are lacking. This study aimed to explore the role of OPCs in mouse MS model experimental autoimmune encephalomyelitis (EAE). Using inducible diphtheria toxin receptor-expressing transgenic mice, platelet-derived growth factor receptor A (PDGFR)+ OPCs were depleted in EAE mice. Surprisingly, OPC depletion in the acute phase improved clinical scores and reduced demyelination. Major histocompatibility complex (MHC) class II was reduced in the spinal cord, whereas astrocyte marker and blood-spinal cord barrier tight junction and adhesion molecule expressions were unaffected after OPC depletion. The numbers of T cells and IL17-expressing Th17 cells were decreased in the spinal cords of the OPC-depleted group. MHC class II expression in spinal cord macrophages was consistently decreased by OPC depletion. These data suggest that in the acute phase of EAE, OPCs are involved in activation of infiltrated macrophages and induce subsequent T cell activation and neuroinflammation. Although the precise mechanisms remain unclear, this implies that OPCs exist not only as the source for oligodendrocytes but also play a pivotal role in central nervous system (CNS) autoimmune inflammation. Table of Contents Image O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=72 SRC="FIGDIR/small/596190v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@98162dorg.highwire.dtl.DTLVardef@d7f92dorg.highwire.dtl.DTLVardef@1280619org.highwire.dtl.DTLVardef@a85907_HPS_FORMAT_FIGEXP M_FIG C_FIG MAIN POINTSO_LIOPC depletion in the acute phase of EAE improved clinical scores and reduced demyelination. C_LIO_LIOPC depletion in the spinal cord suppressed Antigen presentation via MHC class II. C_LIO_LIOPCs are involved in activation of infiltrated macrophages and induce subsequent T cell activation and neuroinflammation. C_LI

neuroscience↗

bioRxiv2022

Extensive gut virome variation and its associations with host and environmental factors in a population-level cohort

Indigenous bacteriophage communities (virome) in the human gut have a huge impact on the gut bacterial communities (bacteriome), but virome variation at a population scale is not fully investigated yet. Here, we analyse the gut virome in a population-level cohort of 4,198 deeply phenotyped individuals. We discovered thousands of high-quality phage genomes including previously uncharacterized ones with different bacterial hosts than known major phage clades. The distribution of host bacteria was a strong determinant for the distribution of phages, and virome diversity was highly correlated with anti-viral defence mechanisms of the bacteriome, such as CRISPR-Cas and restriction-modification systems. We identified 97 various intrinsic/extrinsic factors that significantly affect the virome, including age, sex, lifestyle, and diet, most of which showed consistent associations with both phages and their predicted bacterial hosts. Among the metadata categories, disease and medication had the strongest effects on the virome structure. Overall, these results present a basis to understand the symbiotic communities of bacteria and their viruses in the human gut, which will facilitate the medical and industrial applications of indigenous viruses.

microbiology↗

bioRxiv2022

Emergence of hyper insecticide-resistant dengue vectors in Indochina Peninsula: threats of concomitant knockdown resistance mutations

Aedes aegypti (Linnaeus, 1762) is the main mosquito vector for dengue and other arboviral infectious diseases. Control of this important vector highly relies on the use of insecticides, especially pyrethroids. Nevertheless, the development of pyrethroid resistance is a major obstacle to mosquito/disease control worldwide. Here, we focused on the mutations in the target site of pyrethroid insecticides, voltage-sensitive sodium channel (Vssc), and found that Ae. aegypti collected from Vietnam has the L982W allele in the Vssc at a high frequency (>79%). L982W mutation is located in the highly conserved region of Vssc that is associated with sodium-ion selectivity and permeation rate. Strains having the L982W allele showed similar or even higher levels of resistance to pyrethroids than those having V1016G, a typical knockdown resistance allele in Asia. Furthermore, concomitant mutations L982W+F1534C and V1016G+F1534C were confirmed, and strains having these multiple Vssc mutations exhibited incomparably higher levels of pyrethroid resistance than any other field population ever reported. Molecular modeling analysis confirmed that these concomitant mutant alleles could interfere with approaching pyrethroid to Vssc. Remarkably, >90% of Vssc of Ae. aegypti were occupied by these hyper insecticide-resistant haplotypes in Phnom Penh city, Cambodia. Analysis of whole Vssc coding genes suggested that Vsscs have evolved into stronger resistant forms efficiently through gene recombination events. At this point, L982W has never been detected in Vssc of Ae. aegypti from any other neighboring countries. We strongly emphasize the need to be vigilant about these strong resistance genes spreading to the world through Indochina Peninsula. Significance StatementThe high frequency (>78%) of the L982W allele was detected at the target site of the pyrethroid insecticide, the voltage-sensitive sodium channel (Vssc) of Aedes aegypti collected from Vietnam and Cambodia. Haplotypes having concomitant mutations L982W+F1534C and V1016G+F1534C were also confirmed in both countries, and their frequency was high (>90%) in Phnom Penh, Cambodia. Strains having these haplotypes exhibited substantially higher levels of pyrethroid resistance than any other field population ever reported. The L982W mutation has never been detected in any country of the Indochina Peninsula except Vietnam and Cambodia, but it may be spreading to other areas of Asia, which can cause an unprecedentedly serious threat to the control of dengue fever as well as other Aedes-borne infectious diseases.

neuroscience↗