Biology subjects

Koga, M.

Publications and source records attributed to Koga, M..

8 recordsLinked to original sources

bioRxiv2026

Acute inflammation-mediated attenuation of behavioural sensitization in methamphetamine-sensitized mice via distinct COX-2 and TNF-α pathways

Background and PurposeWhile inflammation has been generally considered to exacerbate symptoms of schizophrenia, some clinical observations suggest that acute inflammation may alleviate positive symptoms. However, animal models often use excessive inflammatory stimuli, and the effects of acute inflammation--comparable to levels observed in patients--remain unknown. Experimental ApproachTo address this, we examined whether acute inflammation induced under relatively mild, clinically relevant conditions suppresses behavioural sensitization in methamphetamine (METH)-sensitized mice, a model of psychostimulant-induced psychosis with relevance to certain aspects of positive symptoms of schizophrenia. We used a repeated METH (1 mg/kg) sensitized model to evaluate the effects of acute inflammation on behavioural sensitization. Acute inflammation was induced via two methods using either lipopolysaccharides (LPS; 1 g/kg) to mimic peripheral immune activation or restraint stress (RS; single 2-h exposure) to model the neuroinflammation induced by psychological stress. LPS doses were adjusted with reference to the magnitude of peripheral cytokine elevation reported in patients, and RS was applied in short single sessions to avoid excessive inflammation. Key ResultsBoth LPS and RS significantly suppressed behavioural sensitization, without inducing other behavioural abnormalities. This suppression was dependent on toll-like receptor-4 activation. LPS-mediated suppression involved cyclooxygenase-2, whereas RS-mediated suppression was linked to the microglia-derived tumour necrosis factor-. LPS did not alter, whereas RS significantly reduced the striatal extracellular dopamine levels. Conclusion and ImplicationsThese findings suggest that acute inflammation suppresses behavioural sensitization through distinct mechanisms depending on the inflammatory trigger, providing a framework for understanding how inflammation may influence psychosis-related processes, with potential relevance to schizophrenia.

pharmacology and toxicology↗

bioRxiv2025

Microglia-dependent LPS preconditioning prevents neuroinflammation-induced behavioral deficits in male mice

Neuroinflammation contributes to psychiatric disorders, but preventive strategies targeting brain immune cells remain unexplored. Here we demonstrate that low-dose lipopolysaccharide (LPS) preconditioning prevents systemic inflammation-induced behavioral abnormalities through microglia-dependent mechanisms in male mice. Mice received preconditioning with 0.2 mg/kg LPS or saline for two consecutive days, followed by high-dose LPS challenge (5 mg/kg) or saline seven days later. Behavioral assessment revealed that preconditioning specifically prevented social preference deficits induced by systemic inflammation (preference score: -0.49{+/-}0.19 vs 0.14{+/-}0.10, p<0.01), while showing limited effects on locomotor activity and depression-like behaviors. Additionally, LPS preconditioning prevented anxiety-like behavior in a chronic corticosterone model and attenuated hippocampal inflammatory gene expression. Immunohistochemical analysis demonstrated that preconditioning suppressed microglial activation in hippocampal CA1 region, particularly reducing PBR/IBA1 ratio (37.5{+/-}2.4% vs 27.6{+/-}2.8%, p<0.01), with less pronounced effects in CA3. Critically, pharmacological microglial depletion using PLX3397 during the preconditioning period completely abolished these protective effects, establishing the causal role of microglia. Flow cytometric analysis revealed preconditioning-induced shifts in brain macrophage subpopulations defined by TMEM119 and CD45 expression patterns. Transcriptomic profiling identified subpopulation-specific responses, with one subset showing LPS-response pathway enrichment despite minimal gene expression changes, while another displayed extensive but functionally non-specific transcriptional alterations. These findings establish microglial preconditioning as a novel preventive strategy for neuroinflammation-induced social behavioral deficits and suggest potential therapeutic applications for psychiatric disorders involving neuroinflammatory components.

neuroscience↗

bioRxiv2024

Structure-activity relationships and crucial mechanisms of the coumarin family as germination inhibitors

Coumarin is produced by various land plants, such as cherry trees, and is known to exhibit a wide range of physiological activities. Notably, one of its primary functions is the inhibition of seed germination. However, the structural basis underlying coumarins germination-inhibitory effect remains poorly understood. In this study, we analyzed the structure-activity relationships of coumarin analogs in two plant species, white clover and Arabidopsis, and demonstrated that the benzene ring and ester bond within the coumarin skeleton constitute the minimal structural requirements for germination inhibition. The inhibitory effects of dihydrocoumarin, which lacks the double bond in the coumarin skeleton, varied among plant species, while those of various other modified coumarin analogs also differed across species. In both plant species, coumarin consistently proved to be one of the most potent inhibitors. Furthermore, the observation that dihydrocoumarin exhibited a strong germination inhibitory effect only in white clover suggests that certain coumarin analogs may act in a species-specific manner. Additionally, the mechanism of coumarin-mediated germination inhibition remains largely unclear. Using RNA-Seq analysis on Arabidopsis seeds, we uncovered a novel and critically important mechanism whereby coumarin suppresses the expression of genes encoding expansins, proteins that are responsible for loosening plant cell walls. This study is significant for understanding how coumarin contributes to plant competition in nature.

plant biology↗

bioRxiv2024

Stress-induced brain extracellular vesicles ameliorate anxiety behaviour.

Extracellular vesicles (EVs), nano particles secreted by all types of cells, serve as a communication network, carrying information through the bloodstream to distant cells1,2. Notably, brain cells secrete EVs that play a crucial role in regulating neurological functions3-5. Meanwhile the brain detects acute stress and activates mechanisms to enhance stress resistance and maintain homeostasis6,7. However, the specific contribution of brain-derived extracellular vesicles (BDEVs) in modulating the stress response remains elusive. Here we found that administration of the acute stress-induced BDEVs to mice reduced anxiety-related behaviours, and this reduction was also induced by the administration of only three microRNAs (miRNAs) (miR-199a-3p, miR-99b-3p and miR-140-5p) included in the acute stress-induced BDEVs. Furthermore, we showed that miR-199a-3p contributes to the mechanism of the anxiolytic effect through the suppression of Mecp2 in neurons. These findings elucidate the role of BDEVs in modulating mental activity under acute stress and provide insights into the underlying molecular mechanisms. Our results open up new avenues for therapeutic strategies in the treatment of anxiety disorders using EVs or miRNAs.

animal behavior and cognition↗

bioRxiv2023

Characterization of an EG.5.1 clinical isolate in vitro and in vivo

EG.5.1 is a subvariant of the SARS-CoV-2 Omicron XBB variant that is rapidly increasing in prevalence worldwide. EG.5.1 has additional substitutions in its spike protein (namely, Q52H and F456L) compared with XBB.1.5. However, the pathogenicity, transmissibility, and immune evasion properties of clinical isolates of EG.5.1 are largely unknown. In this study, we used wild-type Syrian hamsters to investigate the replicative ability, pathogenicity, and transmissibility of a clinical EG.5.1 isolate. Our data show that there are no obvious differences in growth ability and pathogenicity between EG.5.1 and XBB.1.5, and both EG.5.1 and XBB.1.5 are attenuated compared to a Delta variant isolate. We also found that EG.5.1 is transmitted more efficiently between hamsters compared with XBB.1.5. In addition, unlike XBB.1.5, we detected EG.5.1 virus in the lungs of four of six exposed hamsters, suggesting that the virus tropism of EG.5.1 is different from that of XBB.1.5 after airborne transmission. Finally, we assessed the neutralizing ability of plasma from convalescent individuals and found that the neutralizing activity against EG.5.1 was slightly, but significantly, lower than that against XBB.1.5 or XBB.1.9.2. This suggests that EG.5.1 effectively evades humoral immunity and that the amino acid differences in the S protein of EG.5.1 compared with that of XBB.1.5 or XBB.1.9.2 (i.e., Q52H, R158G, and F456L) alter the antigenicity of EG.5.1. Our data suggest that the increased transmissibility and altered antigenicity of EG.5.1 may be driving its increasing prevalence over XBB.1.5 in the human population.

microbiology↗

bioRxiv2019

Estimation of the Hemoglobin Glycation Rate Constant

AimIn a previous study, a method of obtaining mean erythrocyte age (MRBC) from HbA1c and average plasma glucose (AG) was proposed. However, the true value of the hemoglobin glycation constant (kg dL/mg/day), required for this model has yet to be well characterized. Another study also proposed a method of deriving MRBC from erythrocyte creatine (EC). Utilizing these formulae, this study aimed to determine a more accurate estimate of kg.\n\nMethods107 subjects including 31 patients with hemolytic anemia and 76 subjects without anemia were included in this study. EC and HbA1c data were analyzed, and MRBC using HbA1c, AG and the newly-derived constant, kg were compared to MRBC using traditional 51Cr in three patients whose data were taken from previous case studies.\n\nResultA value of 7.0 x 10-6 dL/mg/day was determined for kg. MRBC using HbA1c, AG and kg were found to no be significantly different (paired t-test, p = 0.45) to MRBC using traditional 51Cr.\n\nConclusionskg enables the estimation of MRBC from HbA1c and AG.

physiology↗

bioRxiv2019

A Novel Method for Calculating Mean Erythrocyte Age Using Erythrocyte Creatine

BackgroundsErythrocyte creatine (EC) decreases reflecting erythrocyte age.\n\nMethodsWe developed an EC model, which showed a bi- or mono-exponential relationship between mean erythrocyte age (MRBC) and EC. We reanalyzed the previously published data of 21 patients with hemolytic anemia which included EC and 51Cr half-life.\n\nResultsMRBC and loge EC showed excellent significant linearity (r = -0.9475, p < 0.001), showing that it can be treated as a mono-exponential relationship within the studied range (EC: 1.45 - 11.76 {micro}mol/g Hb). We established an equation to obtain MRBC (days) from EC ({micro}mol/g Hb), MRBC = -22.84 loge EC + 65.83.\n\nConclusionThis equation allows calculation of MRBC based on EC which has practical applications such as the diagnosis of anemia.

physiology↗

bioRxiv2018

Glutathione shapes glutamatergic transmission

Glutamate is the most abundant excitatory neurotransmitter, present at the bulk of cortical synapses, and participating in many physiologic and pathologic processes ranging from learning and memory to stroke. The tripeptide, glutathione, is one third glutamate and present at up to low millimolar intracellular concentrations in brain, mediating antioxidant defenses and drug detoxification. Because of the substantial amounts of brain glutathione and its rapid turnover under homeostatic control, we hypothesized that glutathione is a relevant reservoir of glutamate, and could influence synaptic excitability. We find that drugs which inhibit generation of glutamate by the glutathione cycle elicit decreases in cytosolic glutamate and decreased miniature excitatory post synaptic potential (mEPSC) frequency. In contrast, pharmacologically decreasing the biosynthesis of glutathione leads to increases in cytosolic glutamate and enhanced mEPSC frequency. The glutathione cycle can compensate for decreased excitatory neurotransmission when the glutamate-glutamine shuttle is inhibited. Glutathione may be a physiologic reservoir of glutamate neurotransmitter.\n\nSignificanceGlutathione is the principal antioxidant and redox regulator in cells. In addition to its essential roles in redox homeostasis it functions as cofactors for a multitude of enzymes. We show here that glutathione is a reservoir for synaptic glutamate, the excitatory neurotransmitter in the central nervous system. Deficits in glutathione have been linked to multiple neurodegenerative and neuropsychiatric disorders. Accordingly, agents that restore glutathione-glutamate homeostasis may afford therapeutic benefit.

neuroscience↗