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Hashimoto, N.

Publications and source records attributed to Hashimoto, N..

4 recordsLinked to original sources

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↗

Environmental exosomes: Evidence of extracellular RNA release by aquatic organisms

Aquatic organisms continuously interact with surrounding water, yet whether they release extracellular vesicles remains unknown. We hypothesized that pearl oysters (Pinctada fucata) release exosomes/small extracellular vesicles (sEVs) into the aquatic environment. To this end, we collected exosomes/sEV-sized components by ultrafiltration from tank water and open-sea culture areas. Microscopy revealed abundant vesicles consistent with exosome/sEV size, and RNA sequencing identified oyster-specific piRNAs that matched sequences previously detected in hemolymph exosomes. These findings demonstrated that pearl oysters actively released exosomes containing species-specific nucleic acids into surrounding water. We propose referring to these vesicles as environmental exosomes/environmental sEVs (eExosomes/esEVs). This finding suggests that aquatic exosomes serve as carriers of RNA and may contribute to inter-organismal communication networks. Beyond their functional role, eExosomes/esEVs also hold promise as novel targets for environmental DNA/RNA (eDNA/eRNA) analysis, offering new opportunities for ecological monitoring and biodiversity research.

ecology↗

Sprouty4 is required for Mdm2 regulation of invasion, focal adhesion formation and metastasis in cells lacking p53.

Although the E3 ligase Mdm2 and its homologue and binding partner MdmX are the major regulators of the p53 tumor suppressor protein, it is now evident that Mdm2 and MdmX have multiple functions that are independent of p53. For example, Mdm2 can regulate cell migration, although mechanistic insight into this function is still lacking. Here we show in cells lacking p53 expression that knockdown of Mdm2 or MdmX, as well as pharmacological inhibition of the Mdm2/MdmX complex, not only reduces cell migration and invasion, but also impairs cell spreading and focal adhesion formation. In addition, Mdm2 knockdown decreases metastasis in vivo. Remarkably, Mdm2 modulates the expression of Sprouty4, which is required for the Mdm2 mediated effects on cell migration, focal adhesion formation and metastasis. Our findings describe a molecular mechanism by which the Mdm2-X complex, through Sprouty4, regulates cellular processes leading to decreased metastatic capability independent of p53.

cancer biology↗