Biology subjects

Kida, H.

Publications and source records attributed to Kida, H..

4 recordsLinked to original sources

bioRxiv2025

Riluzole shifts glial responses to protect synapses and memory in Aβ oligomer-treated rats

Soluble A{beta}1-42 (amyloid beta) oligomers are potent neurotoxins that disrupt synaptic function, alter glial responses, and lead to memory impairment in Alzheimers disease (AD). Riluzole, a glutamate modulator approved for amyotrophic lateral sclerosis, reduces neuronal hyperexcitability, yet its in vivo effects on A{beta} oligomer-induced cognitive dysfunction and glial alterations remain incompletely understood. Here, we investigated whether riluzole ameliorates A{beta}1-42 oligomer-induced memory impairment and associated hippocampal pathology. A{beta}1-42 oligomers were bilaterally microinjected into the dorsal CA1 region of rats, followed by daily riluzole administration for seven days. Behavioral analyses revealed that riluzole significantly improved hippocampus-dependent memory, including contextual learning and spatial working memory, without affecting locomotor activity, anxiety-like behavior, or pain sensitivity. At the cellular level, riluzole reduced neuronal A{beta} accumulation and attenuated synaptic and dendritic pathology, while increasing A{beta} association with astrocytes and microglia in parallel with enhanced CD11b-related recognition and lysosomal processing. Notably, reductions in neuronal A{beta} burden were strongly associated with improved learning performance across individual animals. Riluzole also attenuated A{beta}-induced neuronal apoptosis, dendritic degeneration, and dendritic spine loss across the dorsal CA1 sublayers, and limited complement-dependent synaptic elimination by microglia. Although A{beta} oligomers induced robust recruitment of astrocytes and microglia, riluzole did not suppress glial activation; instead, it promoted morphological remodeling and shifted both astrocytes and microglia toward phenotypes associated with neuroprotection. Together, these findings indicate that coordinated remodeling of glial responses links glutamatergic modulation to enhanced amyloid handling, synaptic stability, and recovery of hippocampus-dependent memory under A{beta} oligomer challenge. Significance StatementSoluble A{beta} oligomers impair memory by disrupting synapses and altering glial responses in Alzheimers disease. Although glial activation is often viewed as detrimental, our findings demonstrate that the functional state of glia is a critical determinant of synaptic and cognitive outcomes. Using an A{beta} oligomer-based rat model, we show that the glutamate modulator riluzole restores hippocampus-dependent memory not by suppressing glial recruitment, but by promoting coordinated functional and morphological remodeling of astrocytes and microglia toward phenotypes associated with neuroprotection. These changes are accompanied by enhanced glia-mediated amyloid handling, reduced complement-dependent synaptic elimination, and preservation of dendritic spine integrity. Across individual animals, hippocampus-dependent learning performance was negatively associated with neuronal A{beta} burden, linking glial-mediated amyloid handling to behavioral recovery.

neuroscience↗

bioRxiv2023

Origami-based growing tube model for reproducing shell shapes

Mathematical models for shell morphology have been well-studied in theoretical morphology. The growing tube model proposed by Takashi Okamoto was developed to reproduce heteromorph ammonoids and can generate various shells by changing three parameters: curvature, torsion, and enlarging ratio. Previous studies in theoretical morphology have employed computers to visualize mathematical models. However, computers are not accessible to everyone, and merely observing the graphics of the reproduced shells does not deepen understanding of the mathematical model. Therefore, in this study, we considered using origami, which is inexpensive and readily available, to make users understand mathematical models through hands-on folding. First, we simplified the crease pattern of seashells, originally devised by an origami artist Tomoko Fuse, to create a basic crease pattern. We then identified the crease pattern elements corresponding to the three parameters in the growing tube model and the aperture-apex position determiner. Based on them, we reproduced various shell shapes, including a heteromorph-ammonoid-like shape, with origami. Finally, we investigated the constraints between parameters in the origami-growing tube model. The origami-growing tube model is expected to help disseminate mathematical models and promote theoretical biology.

scientific communication and education↗

bioRxiv2022

2-Thiouridine is a broad-spectrum antiviral nucleoside analogue against positive-strand RNA viruses

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes significant morbidity and mortality worldwide, seriously impacting not only human health but also the global economy. Furthermore, over 1 million cases of newly emerging or re-emerging viral infections, specifically dengue virus (DENV), are known to occur annually. Because no virus-specific and fully effective treatments against these and many other viruses have been approved, they continue to be responsible for large-scale epidemics and global pandemics. Thus, there is an urgent need for novel, effective therapeutic agents. Here, we identified 2-thiouridine (s2U) as a broad-spectrum antiviral nucleoside analogue that exhibited antiviral activity against SARS-CoV-2 and its variants of concern, including the Delta and Omicron variants, as well as a number of other positive-sense single-stranded RNA (ssRNA+) viruses, including DENV. s2U inhibits RNA synthesis catalyzed by viral RNA-dependent RNA polymerase, thereby reducing viral RNA replication, which improved the survival rate of mice infected with SARS-CoV-2 or DENV in our animal models. Our findings demonstrate that s2U is a potential broad-spectrum antiviral agent not only against SARS-CoV-2 and DENV but other ssRNA+ viruses.

microbiology↗

bioRxiv2021

Genome-wide association study reveals putative bacterial risk factors for cavitary Mycobacterium avium complex lung disease

Mycobacterium avium complex (MAC) lung disease is a slowly progressive disease, and its increasing incidence has garnered increased research interests. Cavitary MAC lung disease is associated with a higher mortality rate. Though genetic studies have unraveled the human risk factors, the role of microbial factors on pathogenesis behind the disease remains elusive. In this study, M. avium isolates were collected from sputum specimens of 109 distinct Japanese patients with or without a cavity (60 with a cavity and 49 without cavity) in a hospital located in Osaka prefecture. M. avium genomes were sequenced and searched for DNA motifs associated with cavity formation using a bacterial GWAS. Excluding known macrolide resistance mutations; cavity formation was found to be primarily associated with variants of cytochrome P450 of the CYP139 family, type I polyketide synthase Pks13, and the promoter region of an operon encoding membrane-anchored protease FtsH and folate synthesis pathway enzymes. Cavity risk variants at these three loci were frequent in the MahEastAsia2 lineage among the six lineages detected in M. avium global populations. Furthermore, the study demonstrated a correlation between the cavity risk promoter variant and increased sulfamethoxazole/trimethoprim resistance. Together, these findings suggest that natural variation in the biosynthesis and maintenance processes of M. avium membrane components influences the disease type of MAC lung disease. Although further validation is needed, the bacterial genetic markers listed in the present study could contribute to prognosis prediction based on bacterial genotyping and help develop treatment strategies in the future. IMPORTANCENontuberculous mycobacterial lung disease is of great concern in countries with an increasingly aging population. The disease types can largely be classified into non-cavitary nodular bronchiectasis and cavitary diseases (fibrocavitary, nodular bronchiectasis with cavity) that require different treatment strategies depending on the causal agents. Several studies have reported human risk factors for the disease; however, little efforts were made to investigate the risk factors in nontuberculous mycobacteria. Moreover, molecular genetics experiments have been difficult to search for virulence factors in M. avium, which the population genomics approaches could overcome. Here, the GWAS results suggested variants in three chromosomal loci associated with mycobacterial membrane components as risk factors for cavitary MAC lung disease. These findings could help develop treatment strategies for MAC lung disease in the future.

microbiology↗