Shoichi Shimada

Aversion can arise from a combination of unconditioned stimuli that induce physical discomfort, such as pain and nausea. Chemotherapy-induced side effects, including taste and olfactory aversion, can persist even after treatment has ended, thereby reducing the quality of life. Currently, however, no effective pharmacological interventions exist for treating chemotherapy-induced conditioned aversion learning. Therefore, elucidating its underlying mechanisms is of great importance. In this study, we investigated cisplatin-induced olfactory aversion learning using the two-bottle choice test. Cisplatin was found to induce aversive responses to neutral odorants, namely isoamyl acetate and benzaldehyde. Notably, we obtained two key findings. First, an odor solution that was not aversive in the two-bottle choice test (i.e., distilled water) became aversive to mice when compared with a third novel odor solution that had not been presented in the test. Second, when pairs of three odorants were alternated over an extended period, the mice occasionally shifted their aversive responses as the pairings changed. In clinical practice, patients are exposed to a variety of odors. Thus, the new insights gained from this study on olfactory aversion may help inform the development of novel treatments for chemotherapy-related side effects. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

The subchondral bone plate (SBP) is crucial for joint biomechanics and is implicated in degenerative joint disease. Absolute CT Hounsfield units (HUs) vary with scanner settings, limiting generalisability. We evaluated whether CT-derived relative HU profiling can estimate the location and thickness of the subchondral mineralized interface by comparison with mechanical indentation-derived measurements. Eighteen distal radii from nine formalin-fixed cadaver donors underwent low-dose CT and indentation testing. Post-test scans were registered to pre-test scans so CT- and indentation-based measures were sampled at identical locations. The SBP starting point and thickness were defined from HU attenuation transitions and load–displacement curves, respectively. Association between methods was evaluated with linear mixed-effects models using donor identity as a random intercept and summarised with marginal/conditional R²; agreement was descriptively assessed using Bland–Altman analysis. Inter-observer reliability was assessed using intraclass correlation coefficients. HU-based measures were strongly associated with indentation-derived measures, with fixed-effect slopes of 0.953 for the starting point and 0.988 for thickness, and R²m/R²c values of 0.916/0.918 and 0.912/0.912, respectively. Donor-level clustering effects were minimal. Reliability was good for HU-based measurements and good-to-excellent for indentation-based measurements. Bland–Altman analysis showed smaller bias and narrower limits of agreement for thickness than for the starting point. Relative HU profiling on standard clinical CT provided reproducible estimates of subchondral mineralized boundary features in this ex vivo cadaveric model. These findings support the feasibility of using relative HU transitions as a radiologic surrogate, while further histological and in vivo validation is required before clinical application.

Summary: Dopamine signaling plays critical roles in postnatal brain development, yet the molecular consequences of early dopaminergic disturbance remain incompletely understood. Here, we investigated transcriptomic alterations in the prefrontal cortex (PFC) and striatum (STR) of mice subjected to early postnatal dopaminergic disturbance by 6-hydroxydopamine (6-OHDA) treatment. Using bulk RNA sequencing (RNA-seq) and weighted gene co-expression network analysis (WGCNA), we identified 369 differentially expressed genes (DEGs) in the PFC, 493 DEGs in the STR, and 32 co-expression modules with region-specific expression patterns. Functional enrichment analyses showed that PFC DEGs were associated with cortical development, plasma membrane signaling, and transcriptional regulation, whereas STR DEGs were enriched for striatal development, locomotion, extracellular matrix organization, and amphetamine response. Co-expression network analysis further identified module-specific enrichments related to developmental, synaptic, metabolic, immune-related, and transcriptional programs. DEG sets from both regions also overlapped with genes implicated in attention-deficit/hyperactivity disorder (ADHD) and other neuropsychiatric disorders. Together, these findings reveal region-specific cortico-striatal transcriptomic remodeling following early postnatal dopaminergic disturbance and identify molecular programs that may link developmental dopaminergic perturbation to later behavioral phenotypes. Highlights: Early dopaminergic disturbance reshapes cortico-striatal transcriptomes PFC changes were linked to developmental and transcriptional programs STR changes were linked to locomotion and extracellular matrix programs Network analysis revealed region-specific developmental and synaptic programs

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and restricted repetitive behaviors, yet the contribution of trace elements remains poorly defined. We profiled 21 trace elements in individuals with ASD and identified significantly reduced copper levels, which negatively correlated with social symptom severity. Magnetic resonance imaging revealed decreased white matter volume in ASD, which also correlated with social impairment. To explore the mechanisms, we generated a copper-deficient mouse model that displayed ASD-like behaviors and impaired oligodendrocyte (OL) development. Copper deficiency disrupted hypoxia-inducible factor 1α (HIF1α)–dependent angiogenesis and metabolic regulation in the embryonic brain, leading to oxidative stress, mitochondrial dysfunction, and BCL2 interacting protein 3 (BNIP3)-mediated mitophagy in oligodendrocyte progenitor cells. These processes suppressed mechanistic target of rapamycin kinase (mTOR) signaling, reduced OL-lineage cells, and caused hypomyelination. Restoring mTOR activity rescued OL maturation and improved social behavior in copper-deficient mice. These findings identify a copper-HIF1α-BNIP3-mTOR signaling axis that links trace element imbalance to glial dysfunction and ASD-relevant behavioral phenotypes, providing mechanistic insight into neurodevelopment.

Purpose: This study was aimed at assessing the effects of cerebral sympathetic nervous system activity and renal denervation (RD) on the intrarenal renin-angiotensin system (RAS) and salt-induced nocturnal polyuria (NP).Methods: To establish a mouse model, NP was induced by Nω-nitro-L-arginine methyl ester and a high-salt diet. Mice were subjected to dietary, pharmacological, and RD interventions, with blood pressure, urine output, renal norepinephrine, kidney protein expression, and c-Fos positive cells in the hypothalamic paraventricular nucleus (PVN) assessed using standardized physiological, biochemical, and histological methods.Results: Renal angiotensinogen (AGT) and PVN c-Fos were significantly increased in NP model mice, indicating sympathetic activation. RD lowered renal AGT and the diurnal polyuria index versus sham (1.070±0.091 vs. 1.595±0.136 arbitrary units, P<0.01; 0.182±0.018 vs. 0.338±0.021, P<0.01).Conclusions: Cerebral sympathetic activation may promote intrarenal RAS activity and salt-induced NP; therefore, RD may be a potential therapeutic strategy to improve NP.

Postoperative delirium (POD) is a neurocognitive complication that commonly occurs after cardiac surgery. Despite the association of POD with increased morbidity and mortality, reliable perioperative biomarkers for predicting POD remain scarce. This retrospective observational study investigated whether temporal changes in perioperative redox balance are associated with POD development. Fifty adult patients who underwent elective cardiac surgery at Osaka University Hospital were included. Serum levels of derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) were measured preoperatively, immediately after intensive care unit admission, and on postoperative days 1–4. POD was assessed twice daily using the Intensive Care Delirium Screening Checklist (ICDSC), with an ICDSC score of ≥3 indicating delirium. POD occurred in 18 (36%) out of 50 patients. Compared with non-POD patients, those with POD exhibited higher preoperative d-ROMs levels, a lower BAP/d-ROMs ratio, a transient postoperative increase in BAP, and a relatively higher BAP/d-ROMs ratio during the early postoperative period. Preoperative d-ROMs levels showed a positive correlation with the maximum ICDSC score. In conclusion, perioperative redox dynamics are associated with POD risk and severity. Redox-related markers, particularly d-ROMs, may have potential as biomarkers for identifying patients at higher risk of POD after cardiac surgery, and their clinical utility warrants further prospective validation.