毛利 彰宏

Animal models are essential for studying aversive states such as fear and pain. Facial expressions may provide non-invasive readouts of aversive states in animals. This study investigated whether changes in facial expressions, which are potentially consistent between humans and mice, can serve as objective indicators of fear responses and distinguish fear from pain. We analyzed changes in the facial expressions of mice associated with conditioned fear stress (CFS) using convolutional neural networks (CNNs). Photographs of CFS and control mice were analyzed using four advanced CNN models: VGG16, ResNet50, DenseNet121, and InceptionV3. The CNNs identified CFS mice from facial images under contrasts: control/non-freezing vs CFS/freezing and control/non-freezing vs CFS/non-freezing, with consistently high performance (Control/non-freezing vs CFS/freezing: sensitivity 0.942, specificity 0.929, accuracy 0.935, precision 0.929, AUC 0.966; Control/non-freezing vs CFS/non-freezing: sensitivity 0.912, specificity 0.900, accuracy 0.906, precision 0.902, AUC 0.950). The ability to detect CFS without freezing decreased as stress intensity weakened, from an AUC of 0.950 to 0.701, suggesting that CNNs can detect facial changes depending on the degree of stress exposure. Facial changes were particularly pronounced in freezing mice, further supporting their association with CFS-related emotional responses. During testing, mice were returned to the conditioning chamber without shock; therefore, this facial expression could reflect fear response rather than pain response. These findings demonstrate the potential of CNNs to serve as non-invasive tools for detecting stress-induced affective changes in mice.

High salt (HS) intake is a major risk factor of hypertension and has been implicated in emotional and cognitive decline. On the other hand, dietary supplementation may represent a potential preventive strategy against health risks induced by HS intake. Soybean lecithin is widely used as a phospholipid supplement. Here, we investigated the effects of lysolecithin enriched in lysophosphatidylcholine (>70% of total phospholipids; LPC70) on hypertension and behavioral impairments under high-salt diet (HSD) conditions in mice. To further characterize these effects, we examined changes in prostaglandin (PG)-related pathways by integrating gene expression and lipidomic analyses. Mice were fed an HSD (chow containing 8% NaCl) with or without LPC70 for 10 weeks. HSD elevated systolic blood pressure and impaired social behavior and object recognition memory in mice. Quantitative gene expression analyses revealed that HSD increased renal expression of cyclooxygenase-2 (COX-2) and EP3 (PGE2 receptor), and reduced expression of DP1 (PGD2 receptor) in the prefrontal cortex. LPC70 attenuated these changes in behavior, blood pressure, and PG-related gene expression. Furthermore, lipidomic analyses revealed that HSD reduced circulating arachidonic acid (AA) levels, whereas LPC70 increased AA-derived PG, such as PGE2 and PGD2, in HSD-fed mice. These findings demonstrate that LPC70 may protect against hypertension and behavioral impairments under HSD conditions in mice, potentially in association with modulation of PG signaling. LPC70 may serve as a functional dietary component that reshapes lipid mediator signaling under HSD conditions.

Multiple sclerosis (MS) is a common autoimmune demyelinating disease of the central nervous system (CNS). Although activation of the kynurenine (KYN) pathway has been observed in patients with MS, its pathological significance remains unclear. In this study, we investigated the role of the KYN pathway in MS using an experimental autoimmune encephalomyelitis (EAE) mouse model, a widely recognized animal model of MS. We found an increase in the expression of kynureninase (KYNU), a key enzyme in the KYN pathway that is specifically localized within monocytes in the spinal cord of EAE mice. This was accompanied by a significant accumulation of quinolinic acid (QUIN) in the spinal cord. Importantly, similar increases in KYNU expression and QUIN levels were observed in the spinal cord of proteolipid protein overexpressing mice (PLP-tg mice), another model of demyelination. Notably, KYNU knockout (KO) reduced EAE severity and monocyte recruitment to the spinal cord of EAE model mice. These findings suggest that the increase in KYNU expression and the subsequent accumulation of QUIN may contribute to the exacerbation of MS. Taken together, our results indicate that KYNU could be a novel therapeutic target for MS.

BACKGROUND: Although the number of frozen-thawed blastocysts transfer is increasing worldwide, the live birth rate following blastocyst transfer using assisted reproductive technology remains at 30-60%. Thus, improving the pregnancy rate per transfer is an urgent issue. In a previous retrospective study, we evaluated the use of granulocyte-macrophage colony-stimulating factor (GM-CSF)-containing medium for recovery culture to improve the outcomes of frozen-thawed blastocyst transfers. The results demonstrated that the live birth rates increased by approximately 10% following recovery culture in the GM-CSF-containing culture medium. This study aims to prospectively evaluate whether GM-CSF-containing blastocyst recovery culture following thawing increases live birth. METHODS: This is a multicenter, randomized, parallel-group, active-controlled, single-blind trial. The recruitment target is 750 participants meeting the criteria. Enrolled patients are randomized 1:1 to the GM-CSF-containing culture medium group (test group) or the non-GM-CSF-containing culture medium group (control group). The blastocyst recovery culture after warming was defined as an intervention in this study; frozen-thawed blastocysts will be cultured for 3-7 h in GM-CSF-containing medium (test group) or medium without GM-CSF (control group) followed by blastocyst transfer. The primary outcome will be live birth. We will also evaluate embryo transfer outcomes as secondary efficacy endpoints and evaluate perinatal and neonatal outcomes as a safety endpoint. DISCUSSION: This is the first large-scale prospective study to investigate the efficacy of a GM-CSF-containing medium for frozen-thawed blastocyst transfer. The study findings will provide evidence regarding the efficiency of GM-CSF-containing medium for blastocyst recovery culture after warming. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCT1040240159. Registered on January 6, 2025.

BACKGROUND: Alterations in tryptophan-kynurenine (TRP-KYN) metabolism, which is associated with neuroinflammation, remain unclear in multiple system atrophy (MSA). OBJECTIVE: The aim was to investigate cerebrospinal fluid (CSF) TRP metabolites in MSA and their associations with other biomarkers. METHODS: A total of 51 patients with MSA and 56 controls were included. CSF TRP metabolites, such as KYN, quinolinic acid (QA), and kynurenic acid (KA), along with neurofilament light chain (NfL), glycoprotein nonmetastatic melanoma protein B (GPNMB), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2), were analyzed. RESULTS: Patients with MSA exhibited higher levels of QA, a neuroinflammatory marker, and lower levels of KA, a neuroprotective marker, yielding an elevated QA-to-KA ratio. Neither QA nor KA correlated with clinical scores. GPNMB, sTREM2, and NfL were increased; however, these markers were independent of KYN pathway metabolites. CONCLUSIONS: MSA exhibited a significant imbalance in KYN metabolism, suggesting a shift toward inflammatory processes distinct from classic neuroinflammatory markers. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.