Experimental Animals最新文献

{"title":"Contrasting effects of PHD finger protein 24 (PHF24) on brain morphology of the spontaneous generalized tonic-clonic seizure model; Noda epileptic rat (NER) and Phf24-null rat.","authors":"Yuki Numakura, Miyuu Tanaka, Takeshi Izawa, Jyoji Yamate, Takashi Kuramoto, Tadao Serikawa, Naofumi Kunisawa, Saki Shimizu, Yukihiro Ohno, Mitsuru Kuwamura","doi":"10.1538/expanim.25-0125","DOIUrl":"10.1538/expanim.25-0125","url":null,"abstract":"<p><p>Noda epileptic rat (NER) is a mutant model for epilepsy that exhibits spontaneous generalized tonic-clonic seizure. Epileptogenesis of NER remains to be elucidated; but it is detected an insertion of an endogenous retrovirus sequence in intron 2 of the PHD finger protein 24 (Phf24) gene. PHF24 is widely expressed in the soma of neurons and neuropil in the wild-type rat brain and spinal cord but significantly less expressed in NER. In addition, the characteristic PHF24 expressions were noted in the soma of specific populations of the inhibitory interneurons. Here, we first examined the morphology of the neurons and synapses in the brain of NER to evaluate the epileptogenesis of NER. In NER, the total number of neurons was decreased, but the inhibitory neurons were increased. Inhibitory synapses increased while excitatory synapses tended to decrease in NER. Secondary, we examined Phf24-null rat without symptom of seizures in the same manner and evaluate a contribution of PHF24 to the epileptogeneis of NER. Interestingly, the opposite trend was observed in Phf24-null rats, with a decrease in the inhibitory neurons and synapses, an increase trend in the excitatory synapses. PHF24 is considered to play an important role in maintaining of the inhibitory neurons in the rat brain. We conclude that the reduction of PHF24 might lead to impaired inhibitory signals and increase susceptibility to epilepsy in NER. The histopathological changes of NER in the present study may represent a secondary change to repeated seizures.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"296-305"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13349737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146219125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effect of safflower yellow in mice with cerebral ischemia reperfusion injury.","authors":"Wachiryah Thong-Asa, Chaloemchai Aunkeaw, Panutda Prongfa","doi":"10.1538/expanim.26-0009","DOIUrl":"10.1538/expanim.26-0009","url":null,"abstract":"<p><p>Safflower yellow (SY), a bioactive compound from Carthamus tinctorius L., possesses potent antioxidant and anti-inflammatory properties and may exert protective effects on vulnerable brain regions during acute global ischemia. Therefore, this study aimed to evaluate the neuroprotective effects of SY against cerebral ischemia-reperfusion (IR) injury in mice, focusing on oxidative status, hippocampal neuronal survival, and white matter integrity. Forty male (Institute of Cancer Research) ICR mice were assigned to Sham-veh, IR-veh, IR-SY50, and IR-SY100 groups. Pretreatment with SY or vehicle was performed for 2 weeks before IR induction by 30-min bilateral common carotid artery occlusion and 24-h reperfusion. Brain infarct volume, oxidative status, and histological changes in the hippocampus and corpus callosum (CC) were evaluated. Significantly increased lipid peroxidation and cerebral infarction, depletion of catalase (CAT) activity, selective neuronal death in the Cornus Ammonis 1 (CA1) region, and loss of CC white matter integrity were clearly depicted after IR induction. Pretreatment with SY doses of 50 and 100 mg/kg significantly attenuated brain infarct volume, together with upregulated superoxide dismutase and catalase activities. Histological analysis revealed a dose-dependent therapeutic threshold. Only SY at 100 mg/kg significantly prevented neuronal death in the CA1 region and preserved CC white matter integrity. Pretreatment with SY exhibits neuroprotective effects against IR primarily by enhancing endogenous antioxidant defenses. Crucially, while biochemical improvements are achievable at lower doses, a higher therapeutic dose is required to preserve neuronal and white matter structural integrity in selectively vulnerable brain regions.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"357-366"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13349746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147573053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of autophagy through Sirt1/AMPK/mTOR mediates the protective effects of fraxin against insulin resistance and steatosis in rats.","authors":"Yang Li, Xinchang Feng, Lingpeng Zheng","doi":"10.1538/expanim.25-0105","DOIUrl":"10.1538/expanim.25-0105","url":null,"abstract":"<p><p>Insulin resistance (IR) and hepatic steatosis are key pathological features of type 2 diabetes mellitus (T2DM). Fraxin, a natural flavonoid with potential metabolic regulatory properties, has been proposed to modulate metabolic disorders. This study aimed to investigate whether fraxin protects against IR and steatosis via Sirt1/AMPK/mTOR-mediated autophagy activation. A T2DM rat model was established using high-fat diet (HFD) feeding combined with streptozotocin (STZ) injection. Rats were treated with fraxin (25 or 50 mg/kg) for 4 weeks, followed by assessment of fasting blood glucose (FBG), insulin (FINS), HOMA-IR index, serum lipid profiles and liver function. Histopathological examination (H&E and Oil Red O staining) evaluated hepatic steatosis. BRL 3A cells exposed to palmitic acid (PA) were treated with fraxin (40 or 80 µM), and glucose uptake, lipid accumulation, and protein expression (IRS-1 phosphorylation, GLUT-2 translocation, autophagy markers and Sirt1/AMPK/mTOR pathway components) were analyzed. The specific autophagy inhibitor chloroquine (CQ) was used to verify whether the regulatory effects of fraxin were dependent on autophagy activation. Fraxin significantly reduced FBG, FINS, HOMA-IR, and dyslipidemia in diabetic rats. In PA-treated BRL 3A cells, fraxin enhanced glucose uptake, reduced lipid droplets, and restored IRS-1 phosphorylation and GLUT-2 membrane localization. Mechanistically, fraxin activated autophagy and modulated the Sirt1/AMPK/mTOR pathway, which were abolished by the Sirt1 inhibitor EX527. In conclusion, fraxin alleviates IR and hepatic steatosis in HFD/STZ-induced diabetic rats by activating autophagy through Sirt1/AMPK/mTOR pathway, suggesting its potential as a therapeutic agent for diabetes-associated metabolic disorders.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"277-287"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13349743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of plant flavonoids and selenium on pancreatic hormones and glucose homeostasis in autoimmune thyroiditis.","authors":"Khasan Kayumov, Lubov Kuchkarova, Dilnoza Romanova, Szczuko Małgorzata, Sevara Berdiyorova, Nurali Ergashev, Irodakhon Karimova, Umida Yusupova, Gulchehra Djabbarova, Sobitjon Mirzakulov, Anna Bokova, Nurshat Murtazayeva, Manzura Agzamova, Komila Eshbakova, Bakhrom Komilov, Aziz Kobilov","doi":"10.1538/expanim.26-0007","DOIUrl":"10.1538/expanim.26-0007","url":null,"abstract":"<p><p>Autoimmune thyroiditis (AIT) is a systemic autoimmune disorder that extends beyond thyroid dysfunction and is associated with disturbances in pancreatic endocrine secretion and glucose metabolism. The present study aimed to evaluate the effects of selected plant flavonoids-dihydroquercetin, chrysoeriol, luteolin, resveratrol, kaempferol, and thamiflaside-administered alone or in combination with selenium on pancreatic hormone secretion, glycemic control, and hepatic glycogen content in an experimental rat model of AIT. AIT was induced in male Wistar rats using thyroglobulin and Freund's adjuvant. After confirmation of autoimmune thyroiditis, animals received flavonoid treatment (20 mg/kg body weight), with or without selenium, for 14 days. Serum concentrations of insulin, glucagon, amylin, and somatostatin were determined by immunoassay. Glycated hemoglobin (HbA1c) was measured as an indicator of long-term glycemic control, and hepatic glycogen content was assessed in liver homogenates. AIT induction resulted in marked metabolic dysregulation characterized by reduced insulin and amylin secretion, elevated glucagon levels, impaired somatostatin regulation, increased HbA1c, and depletion of hepatic glycogen stores. Flavonoid treatment produced compound-specific corrective effects. Luteolin and kaempferol, particularly in combination with selenium, showed the strongest efficacy by restoring pancreatic hormone balance, reducing hyperglucagonemia, improving HbA1c levels, and replenishing hepatic glycogen toward physiological ranges. Dihydroquercetin and chrysoeriol exerted moderate protective effects, whereas resveratrol and thamiflaside showed limited efficacy. In conclusion, autoimmune thyroiditis induces significant disturbances in pancreatic endocrine function and hepatic glucose metabolism, while flavonoid-selenium combinations may represent promising strategies for correcting AIT-associated metabolic dysfunctions.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"367-382"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13349736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147573060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post stress sensory contact with a male mouse is associated with altered social behavior in a female vicarious social defeat stress model.","authors":"Yuhei Yajima, Aki Takahashi, Atsushi Toyoda","doi":"10.1538/expanim.25-0112","DOIUrl":"10.1538/expanim.25-0112","url":null,"abstract":"<p><p>Depression affects females more than males, with responses to antidepressants also exhibiting a distinct difference between sexes. Stress models in rodents have predominantly been developed for males, and their application in females remains challenging. This study investigated how post stress sensory contact with male mice affects the behavioral outcomes of female C57BL/6JJcl (B6) mice subjected to vicarious social defeat stress (VDS). We compared three types of VDS paradigms in female mice: the conventional paradigm and two adapted protocols that eliminated sensory contact with male ICR mice during the post-stress period under either single-housed (SH) or pair-housed (PH) conditions. In the conventional paradigm, female B6 mice did not exhibit a significant increase in social avoidance. In contrast, in the adapted paradigm, social avoidance behavior was observed in the PH group, indicating that post stress sensory contact with male ICR affects the stress susceptibility of female VDS model. Furthermore, the estrous cycle stage did not affect social avoidance behavior in each group. Next, we compared two different housing conditions to examine the appropriate method for eliminating sensory contact in female VDS model. SH mice showed reduced feed intake, increased water consumption, and attenuated body weight gain, regardless of VDS exposure. These findings suggest that post-stress sensory contact with a male mouse may influence social behavior in female mice exposed to VDS. The present study highlights the potential impacts of these experimental variables when interpreting behavioral outcomes in female VDS models.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"334-342"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13349745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of post-weaning diet on hibernation occurrence in Syrian hamsters.","authors":"Akari Yamauchi, Sachiyo Enju, Kanako Sone, Nanaka Matsuoka, Yutaka Tamura, Yoshifumi Yamaguchi","doi":"10.1538/expanim.26-0003","DOIUrl":"10.1538/expanim.26-0003","url":null,"abstract":"<p><p>Mammalian hibernation is an adaptive strategy for surviving harsh cold seasons and food scarcity by suppressing the metabolic rate and thermogenesis. The Syrian hamster (Mesocricetus auratus) (hereafter termed as hamsters), a small mammalian hibernator, hibernates upon exposure to winter-like, short-photoperiod and cold (SP-Cold) conditions throughout a year in a laboratory, and therefore is a useful animal model obtained from a commercial breeder to study mechanisms of hibernation. However, the rates of hibernation occurrence often vary among experiments and facilities, the reason for which is largely unclear. Here we examined the effects of diet given to hamsters during post-weaning stages on hibernation occurrence. Hamsters fed either a high-nutrient (H) diet suitable for reproduction or a standard (STD) diet during the post-weaning period (from 3 or 4 weeks of age to sexual maturation) were exposed to winter-like conditions, and the occurrence of hibernation was assessed. Females showed a higher hibernation induction rate (over 80%) regardless of the post-weaning diet type than males. Approximately half (52%) of the males fed the STD diet from 3 weeks hibernated, whereas males fed the STD diet from 4 weeks or the H diet showed markedly lower hibernation induction rates (≤33%). These results suggest that female Syrian hamsters are more prone to hibernation than males and that the hibernation induction rate in male hamsters is influenced by diet during a critical developmental window between 3 and 4 weeks of age.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"322-333"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13349742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Menstrual cycles, lifespan, and anti-Müllerian hormone in cynomolgus monkeys.","authors":"Akie Takebayashi, Shunichiro Tsuji, Tadashi Sankai, Chizuru Iwatani, Hideaki Tsuchiya, Masatsugu Ema, Takashi Murakami","doi":"10.1538/expanim.25-0098","DOIUrl":"10.1538/expanim.25-0098","url":null,"abstract":"<p><p>The cynomolgus monkey (Macaca fascicularis) is an important experimental animal; however, its menstrual patterns, lifespan, and age-related changes in anti-Müllerian hormone (AMH) levels remain poorly characterized. This study aimed to analyze these factors and evaluate the usefulness of Cynomolgus monkeys in ovarian function research. The age at menarche was examined in 21 cynomolgus monkeys, and the age at menopause and age at death were tracked in another 22 postmenopausal monkeys. In addition, AMH levels were analyzed in 74 cynomolgus monkeys aged 0 to 33 years to evaluate ovarian reserve throughout their lives. Results showed a mean age at menarche of 3.69 ± 2.51 years, menopause at 27.00 ± 2.50 years, and a mean age at death of 32.04 ± 5.33 years. AMH levels throughout life showed a weak negative correlation with age. These findings suggest that changes in ovarian reserve throughout the life span of cynomolgus monkeys are similar to those in humans. To our knowledge, this study is the first to analyze menstruation, lifespan, and lifelong AMH levels in cynomolgus monkeys. Ovarian function throughout life, including childhood and postmenopause, was similar to that in humans, suggesting cynomolgus monkeys may be a useful experimental model.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"234-240"},"PeriodicalIF":2.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PacBio long-read amplicon sequencing of dog leukocyte antigen genes at full-length level in beagle dogs.","authors":"Hiroya Konno, Jiro Miyamae, Rei Kajitani, Kazuto Kugou, Hiroko Kataoka, Makoto Akai, Tomomichi Ishizaka, Katsuyoshi Chiba","doi":"10.1538/expanim.25-0111","DOIUrl":"10.1538/expanim.25-0111","url":null,"abstract":"<p><p>The major histocompatibility complex (MHC) plays a critical role in individual immune responses and susceptibility to various conditions, including autoimmune diseases and drug reactions. In dogs, the canine MHC (dog leukocyte antigen, DLA) polymorphism is key to understanding immune mechanisms, but technical challenges have impeded its comprehensive genetic analysis. This study addressed these issues by using a novel DLA genotyping method combining long-range PCR and PacBio single-molecule real-time sequencing to analyze the full-length DLA class I and II gene sequences in 83 beagle dogs from two different strains (TOYO and Marshall), which are commonly used as laboratory animals. As a result of genotyping using the full-length sequences, 9, 5, 2, 6, and 8 extended alleles were newly discovered for the DLA class I genes in DLA-88, DLA-12, DLA-88L, DLA-64, and DLA-79, respectively. For the DLA class II genes, 11, 18, 12, and 8 extended alleles were newly discovered in DLA-DRA, DLA-DRB1, DLA-DQA1, and DLA-DQB1, respectively. There were 25 haplotypes consisting of extended alleles, in contrast to only 10 haplotypes classified using only peptide binding site sequences. Furthermore, comparisons between the strains revealed differences in haplotype frequencies and genetic differentiation. The full-length analysis also provided preliminary insights into regulatory elements, such as promoter and CpG island polymorphisms in DLA-DQB1. The results of this research have important implications for the understanding of the relationship between DLA polymorphism at full length and individual immune responses in dogs.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"250-261"},"PeriodicalIF":2.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative network pharmacology and experimental study of Qingda granule in hypertension-induced endothelial dysfunction.","authors":"Yanyan Yang, Qiurong Xie, Jingyi Zeng, Meizhu Wu, Daxin Chen, Wenqiang Zhang, Chenyu Lai, Aling Shen, Dawei Lian, Jun Peng","doi":"10.1538/expanim.25-0080","DOIUrl":"10.1538/expanim.25-0080","url":null,"abstract":"<p><p>Endothelial dysfunction (ED) plays a pivotal role in the pathogenesis of hypertension and its associated vascular complications. Qingda granule (QDG) exhibits significant antihypertensive properties and demonstrates therapeutic potential in ameliorating vascular dysfunction. This study aimed to explore QDG's role in alleviating endothelial injury in hypertension. An L-NAME (Nω-Nitro-L-arginine methyl ester)-induced hypertensive mouse model was used to evaluate the effects of QDG on blood pressure and endothelial function. Endothelial function was assessed through histological analysis, nitric oxide (NO) quantification, and vascular response measurements. To explore underlying mechanisms, network pharmacology was conducted using databases such as HERB, SwissTargetPrediction and STRING. Key pathways related to inflammation and cell adhesion were identified. Based on these findings, immunohistochemical staining was conducted to analyze the expression of phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 (p-NF-κB p65), NF-κB p65, intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α) in vascular tissues. QDG treatment significantly reduced blood pressure, increased NO levels, and enhanced endothelial nitric oxide synthase (eNOS) expression in L-NAME-induced hypertensive mice, indicating its potential to restore endothelial function. Experimental validation further confirmed that QDG markedly suppressed the expression of p-NF-κB p65, TNF-α, and ICAM-1 in vascular tissues. These results suggest that QDG alleviates hypertension-induced ED primarily by inhibiting inflammation and endothelial adhesion via the NF-κB signaling pathway. Overall, QDG presents a promising therapeutic candidate for managing hypertension and its vascular complications.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"131-143"},"PeriodicalIF":2.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body weight loss without reduction in food consumption observed in cynomolgus monkeys during non-clinical toxicity studies.","authors":"Kazuaki Takahashi, Norio Hike, Hiroyuki Ogura, Takayuki Okamura, Dai Yamamoto, Junko Sato","doi":"10.1538/expanim.25-0047","DOIUrl":"10.1538/expanim.25-0047","url":null,"abstract":"<p><p>In pharmaceutical development, weight loss is occasionally observed in monkeys during non-clinical toxicity studies and can be difficult to differentiate from drug effects. This study retrospectively analyzed data from control group monkeys without drug treatment to investigate the incidence of weight loss and its physiological and pathological characteristics. We also investigated potential improvements through enhanced animal welfare. In the 4- and 13-week toxicity studies conducted at the test facility from 2010 to 2022, 684 control group monkeys were investigated. Among them, 3 animals in the 4-week toxicity studies and 5 animals in the 13-week toxicity studies showed a weight change rate of less than -10%, resulting in an incidence rate of 1.2%. However, these animals had adequate food consumption. Animals in the 4-week toxicity studies showed signs of stress in histopathology. Additionally, 2/3 animals in the 4-week toxicity studies had decreased blood glucose levels and 1/5 animal in the 13-week toxicity study fell into a crouching posture, suggesting hypoglycemia that was alleviated with glucose administration, indicating stress-induced metabolic abnormalities. From 2015, an enrichment program was implemented to improve animal welfare. Prior to this program, 2.4% of animals showed a weight change rate of less than -10%, which dropped to 0.25% post-implementation, suggesting the program's effectiveness in reducing stress. These results clarify the characteristics of animals that lose weight during toxicity studies and suggest that improving animal welfare can reduce the incidence rate.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"121-130"},"PeriodicalIF":2.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}