IF 5.2 2区生物学

Cells Pub Date : 2025-09-15 DOI: 10.3390/cells14181443

Dario Troise, Barbara Infante, Silvia Mercuri, Bengt Lindholm, Karolina Kublickiene, Giovanni Stallone

{"title":"Exploring the Immunological Landscape of Ischemia/Reperfusion Injury and Graft Rejection in Kidney Transplantation: Shared Mechanisms and Insights.","authors":"Dario Troise, Barbara Infante, Silvia Mercuri, Bengt Lindholm, Karolina Kublickiene, Giovanni Stallone","doi":"10.3390/cells14181443","DOIUrl":"10.3390/cells14181443","url":null,"abstract":"Background: Ischemia/reperfusion injury (IRI) is considered one of the major risk factors involved in the development of delayed graft function that significantly impacts both the early and long-term function of allografts due to its harmful effects on cells.Purpose: This narrative review aims to explore the emerging aspects of IRI in organ transplantation, focusing on the still unclear relationships between IRI and the development of both T-cell-mediated and/or antibody-mediated rejections.Key findings: Recently, efforts aimed at increasing the knowledge of the mechanisms involved have revealed that IRI is connected to rejection processes through a complex of interconnected pathways. These pathways affect both the viability and the metabolism of immune cells, ultimately influencing graft outcomes. Therefore, these pathways demonstrate the complexity of immune responses after transplantation and play a role in both acute and chronic rejection processes.Conclusions: Improving graft outcomes requires an understanding of the multifaceted relationship between IRI and immune-mediated rejection, which is critical to improve graft outcomes. Further research is needed to clarify these mechanisms and develop targeted strategies to mitigate IRI and its impact on transplant rejection.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 18","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Complex Role of the Complement C3a Receptor (C3aR) in Cerebral Injury and Recovery Following Ischemic Stroke. 补体C3a受体（C3aR）在缺血性脑卒中后脑损伤和恢复中的复杂作用

IF 5.2 2区生物学

Cells Pub Date : 2025-09-15 DOI: 10.3390/cells14181440

Naseem Akhter, Ateeq Lambay, Reema Almotairi, Abdullah Hamadi, Kanchan Bhatia, Saif Ahmad, Andrew F Ducruet

{"title":"The Complex Role of the Complement C3a Receptor (C3aR) in Cerebral Injury and Recovery Following Ischemic Stroke.","authors":"Naseem Akhter, Ateeq Lambay, Reema Almotairi, Abdullah Hamadi, Kanchan Bhatia, Saif Ahmad, Andrew F Ducruet","doi":"10.3390/cells14181440","DOIUrl":"10.3390/cells14181440","url":null,"abstract":"The Complement C3a Receptor (C3aR) plays a multifaceted role along the varying temporal phases of brain injury following cerebral ischemia. C3aR is a G-protein-coupled receptor (GPCR) that binds to its ligand, C3a an anaphylatoxin generated during activation of the complement cascade. During ischemia, complement is activated as part of the initial inflammatory response, with C3aRs playing a time-dependent role in both brain injury and repair mechanisms. In the acute phase (minutes to hours post-ischemia), C3aR activation promotes the recruitment of immune cells and the release of chemokines and cytokines, driving blood-brain barrier (BBB) permeability and brain edema. During the subacute phase (hours to days post-ischemia), C3aR continues to modulate immune cell activity, worsening secondary brain injury, although emerging evidence suggests that C3aR activation in this phase may also aid in the clearance of cellular debris and cell survival. In the chronic phase (days to weeks post-ischemia), chronically elevated C3aR activity can prolong neuroinflammation and impair recovery, whereas controlled C3aR signaling in the subacute/chronic phase can activate reparative pathways (e.g., microglial phagocytosis, astrocyte trophic support). As a result, targeting the C3aR requires careful timing to optimize its benefits. Given the dual impact of C3aR activation, which serves to exacerbate injury in the acute phase but supports repair beginning in the subacute and chronic phases, a targeted therapeutic approach should focus on context- and time-dependent modulation of the C3a/C3aR axis. This strategy would involve blocking the C3aR during the acute phase to reduce inflammation and BBB breakdown while controlling C3a signaling in later phases to promote tissue repair.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 18","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Homocysteine-Mediated Neuronal Pyroptosis Contributes to Brain Injury in Heatstroke Rats by Activating the m⁶A-YTHDF2-NLRP3 Pathway. 同型半胱氨酸介导的神经元焦亡通过激活m6A-YTHDF2-NLRP3通路参与中暑大鼠脑损伤

IF 5.2 2区生物学

Cells Pub Date : 2025-09-15 DOI: 10.3390/cells14181437

Shijia Zhang, Fang Xie, Xue Wang, Zhaowei Sun, Ling Zhang, Weiwei Liu, Xiaobing Chen, Lingjia Qian, Yun Zhao

{"title":"Homocysteine-Mediated Neuronal Pyroptosis Contributes to Brain Injury in Heatstroke Rats by Activating the m6A-YTHDF2-NLRP3 Pathway.","authors":"Shijia Zhang, Fang Xie, Xue Wang, Zhaowei Sun, Ling Zhang, Weiwei Liu, Xiaobing Chen, Lingjia Qian, Yun Zhao","doi":"10.3390/cells14181437","DOIUrl":"10.3390/cells14181437","url":null,"abstract":"Heat stroke (HS) is a life-threatening condition that leads to neuronal injury, particularly in the prefrontal cortex, though its mechanisms remain unclear. In this study, we established a rat HS model and observed significant inflammatory responses and neuronal pyroptosis in the prefrontal cortex 6 h post-heat exposure, with the injury severity increasing over time. Mechanistically, HS activated the caspase-1/GSDMD-dependent pyroptosis pathway through NLRP3 inflammasome activation, resulting in IL-1β and IL-18 release. Additionally, HS caused a marked increase in homocysteine (Hcy) levels in both the serum and the prefrontal cortex, accompanied by reduced expression of the Hcy metabolic enzymes MTHFR and CSE, suggesting Hcy metabolism disruption. In vitro, Hcy induced pyroptosis in PC12 cells, elevating IL-1β, IL-18, and LDH levels. Notably, the NLRP3 inhibitor MCC950 mitigated this effect by reducing IL-18 and LDH release. Reducing Hcy in vivo alleviated neuronal pyroptosis and counteracted the YTHDF2-mediated decrease in NLRP3 mRNA m6A modification. Hcy reduced global m6A modification, YTHDF2 expression, and NLRP3 m6A modification in PC12 cells. This study reveals that the activation of a novel m6A-YTHDF2-NLRP3 pathway by Hcy underlies HS-induced neuronal injury, suggesting potential therapeutic targets for HS intervention.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 18","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regional Expression of Dystrophin Gene Transcripts and Proteins in the Mouse Brain. 小鼠脑中肌营养不良蛋白基因转录本和蛋白的区域表达。

IF 5.2 2区生物学

Cells Pub Date : 2025-09-15 DOI: 10.3390/cells14181441

Konstantina Tetorou, Artadokht Aghaeipour, Shunyi Ma, Talia Gileadi, Amel Saoudi, Pablo Perdomo Quinteiro, Jorge Aragón, Maaike van Putten, Pietro Spitali, Cecilia Montanez, Cyrille Vaillend, Jennifer E Morgan, Federica Montanaro, Francesco Muntoni

{"title":"Regional Expression of Dystrophin Gene Transcripts and Proteins in the Mouse Brain.","authors":"Konstantina Tetorou, Artadokht Aghaeipour, Shunyi Ma, Talia Gileadi, Amel Saoudi, Pablo Perdomo Quinteiro, Jorge Aragón, Maaike van Putten, Pietro Spitali, Cecilia Montanez, Cyrille Vaillend, Jennifer E Morgan, Federica Montanaro, Francesco Muntoni","doi":"10.3390/cells14181441","DOIUrl":"10.3390/cells14181441","url":null,"abstract":"Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease caused by mutations in the DMD gene, leading to muscle degeneration and shortened life expectancy. Beyond motor symptoms, DMD patients frequently exhibit brain co-morbidities, linked to loss of brain-expressed dystrophin isoforms: most frequently Dp427 and Dp140, and occasionally Dp71 and Dp40. DMD mouse models, including mdx5cv and mdx52, replicate key aspects of the human cognitive phenotype and recapitulate the main genotypic categories of brain phenotype. However, the spatio-temporal expression of brain dystrophin in mice remains poorly defined, limiting insights into how its deficiency disrupts brain development and function. We systematically mapped RNA and protein expression of brain dystrophin isoforms (Dp427 variants, Dp140, Dp71, and Dp40) across brain regions and developmental stages in wild-type mice. Dp427 isoforms were differentially expressed in the adult brain, with Dp427c enriched in the cortex, Dp427p1/p2 in the cerebellum, and Dp427m was also detected across specific brain regions. Dp140 was expressed at lower levels than Dp427; Dp71 was the most abundant isoform in adulthood. Dp140 and Dp71 displayed dynamic developmental changes, from E15 to P60, suggesting stage-specific roles. We also analysed mdx5cv mice lacking Dp427 and mdx52 mice lacking both Dp427 and Dp140. Both models had minimal Dp427 transcript levels, likely due to the nonsense-mediated decay, and neither expressed Dp427 protein. As expected, mdx52 mice lacked Dp140, confirming their genotypic relevance to human DMD. Our study provides the first atlas of dystrophin expression in the wild-type mouse brain, aiding understanding of the anatomical basis of behavioural and cognitive comorbidities in DMD.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 18","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Skin Barrier: A System Driven by Phase Separation. 皮肤屏障：一个由相分离驱动的系统。

IF 5.2 2区生物学

Cells Pub Date : 2025-09-15 DOI: 10.3390/cells14181438

Fengjiao Yu, Lu Leng, Haowen Wang, Mengmeng Du, Liang Wang, Wenhua Xu

{"title":"The Skin Barrier: A System Driven by Phase Separation.","authors":"Fengjiao Yu, Lu Leng, Haowen Wang, Mengmeng Du, Liang Wang, Wenhua Xu","doi":"10.3390/cells14181438","DOIUrl":"10.3390/cells14181438","url":null,"abstract":"The mammalian epidermis forms a critical barrier against environmental insults and water loss. The formation of its outermost layer, the stratum corneum, involves a rapid terminal differentiation process that has traditionally been explained by the \"bricks and mortar\" model. Recent advances reveal a more dynamic mechanism governed by intracellular liquid-liquid phase separation (LLPS). This review proposes that the lifecycle of the granular layer is orchestrated by LLPS. Evidence is synthesized showing that keratohyalin granules (KGs) are biomolecular condensates formed by the phase separation of the intrinsically disordered protein filaggrin (FLG). The assembly, maturation, and pH-triggered dissolution of these condensates are essential for cytoplasmic remodeling and the programmed flattening of keratinocytes, a process known as corneoptosis. In parallel, an LLPS-based signaling pathway is described in which the kinase RIPK4 forms condensates that activate the Hippo pathway, promoting transcriptional reprogramming and differentiation. Together, these structural and signaling condensates drive skin barrier formation. This review further reinterprets atopic dermatitis, ichthyosis vulgaris, and Bartsocas-Papas syndrome as diseases of aberrant phase behavior, in which pathogenic mutations alter condensate formation or material properties. This integrative framework offers new insight into skin biology and suggests novel opportunities for therapeutic intervention through biophysics-informed biomaterial and regenerative design.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 18","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modeling Synucleinopathy Using hESC-Derived Cerebral Organoids. 利用hesc衍生的脑类器官模拟突触核蛋白病。

IF 5.2 2区生物学

Cells Pub Date : 2025-09-15 DOI: 10.3390/cells14181436

So Jin Kim, Won Hee Jung, Mu Seog Choe, Ye Seong Jeon, Min Young Lee

{"title":"Modeling Synucleinopathy Using hESC-Derived Cerebral Organoids.","authors":"So Jin Kim, Won Hee Jung, Mu Seog Choe, Ye Seong Jeon, Min Young Lee","doi":"10.3390/cells14181436","DOIUrl":"10.3390/cells14181436","url":null,"abstract":"Animal and cellular models harboring SNCA gene mutations have been instrumental in synucleinopathy, but faithful human brain models remain limited. Here, we report the development of a human cerebral organoid (CO) model of synucleinopathy carrying the Ala53Thr mutation in SNCA (SNCAA53T). Using a human embryonic stem cell (hESC) line overexpressing SNCAA53T (A53T hESC line), we generated COs (A53T COs) that recapitulate hallmark features of synucleinopathy. These A53T COs exhibited elevated α-synuclein (α-Syn) expression, the increased phosphorylation of α-Syn, and Lewy body-like aggregations. Notably, we also observed the increased expression of phosphorylated tau and neurofibrillary tangle-like silver deposits, although amyloid β expression and accumulation remained unchanged. To evaluate the utility of this model in drug screening, we treated A53T COs with synuclean D (SynD), an inhibitor of α-Syn aggregation, which significantly reduced both α-Syn and tau phosphorylation without affecting total α-Syn levels. Together, our findings establish a robust hESC-derived synucleinopathy CO model harboring the SNCAA53T mutation, demonstrating its potential as a valuable tool for therapeutic drug screening.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 18","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inflammation-Driven Molecular Ageing in Chronic Inflammatory Skin Diseases: Is There a Role for Biologic Therapies? 慢性炎症性皮肤病中炎症驱动的分子老化：生物治疗是否有作用？

IF 5.2 2区生物学

Cells Pub Date : 2025-09-15 DOI: 10.3390/cells14181442

Klara Andrzejczak, Agata Sternak, Wiktor Witkowski, Małgorzata Ponikowska

引用次数: 0

Predictive Role of MicroRNAs in the Diagnosis and Management of Patients with Crohn's Disease: A Clinician's View. microrna在克罗恩病诊断和治疗中的预测作用：临床医生的观点

IF 5.2 2区生物学

Cells Pub Date : 2025-09-13 DOI: 10.3390/cells14181435

Christian Prinz, Leonard Fehring

{"title":"Predictive Role of MicroRNAs in the Diagnosis and Management of Patients with Crohn's Disease: A Clinician's View.","authors":"Christian Prinz, Leonard Fehring","doi":"10.3390/cells14181435","DOIUrl":"10.3390/cells14181435","url":null,"abstract":"Crohn's disease (CD), also known as terminal ileitis, has been the focus of gastroenterological diagnostics and therapy for decades. Although significant therapeutic progress has been made in recent years, largely due to an improved understanding of the pathophysiology and evolving treatment strategies for Crohn's disease, many new antibody-based therapies demonstrate clinical response rates of only 30-50%. Predictive biomarkers for differential therapeutic responses may therefore be critical for personalized treatment selection, but such markers have not yet been clinically validated for the majority of patients treated with prednisone or monoclonal antibodies targeting integrin pathways, TNF-α, or IL-23. In this review, the diagnostic potential of microRNA (miRNA) dysregulation in patients with Crohn's disease is explored, emphasizing the potential utility of specific miRNA expression profiles in guiding targeted therapy. Notably, reduced expression of miR-29 is associated with planned treatment using ustekinumab (an IL-23 signaling inhibitor), elevated miR-23a levels in inflamed tissue may inform the use of TNF-α inhibitors, increased miR-155 expression is relevant for patients considered for JAK inhibitor therapy, and altered levels of miR-126 and miR-486 may support the selection of vedolizumab. Assessment of these dysregulated miRNAs-such as through comparative profiling in inflamed versus non-inflamed tissue from the same patients-could serve as a predictive biomarker panel to optimize individualized immunosuppressive treatment strategies in Crohn's disease. We also examine the role of microRNAs in regulating TRP channels and their involvement in the mechanisms of action of selected complementary medicines.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 18","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Defined Composition of Culture Media Promotes Rodent Neonatal Cardiomyocyte Maturation and Enables Functional Neuro-Cardiac Co-Culture. 确定的培养基组成促进啮齿动物新生心肌细胞成熟并实现功能性神经心脏共培养。

IF 5.2 2区生物学

Cells Pub Date : 2025-09-13 DOI: 10.3390/cells14181434

Giulia Borile, Lolita Dokshokova, Nicola Moro, Antonio Campo, Valentina Prando, Jose L Sanchez-Alonso, Julia Gorelik, Giuseppe Faggian, Marco Mongillo, Tania Zaglia

{"title":"Defined Composition of Culture Media Promotes Rodent Neonatal Cardiomyocyte Maturation and Enables Functional Neuro-Cardiac Co-Culture.","authors":"Giulia Borile, Lolita Dokshokova, Nicola Moro, Antonio Campo, Valentina Prando, Jose L Sanchez-Alonso, Julia Gorelik, Giuseppe Faggian, Marco Mongillo, Tania Zaglia","doi":"10.3390/cells14181434","DOIUrl":"10.3390/cells14181434","url":null,"abstract":"Neonatal rodent cardiomyocytes (CMs) are a mainstay of in vitro cardiac research, yet their immature phenotype limits the study of key physiological processes such as excitation-contraction coupling (ECC) and sympathetic modulation. Here, we present a defined low-glucose, serum-free (LGSF) culture protocol that drives the structural and functional maturation of neonatal CMs and supports their integration into functional neuro-cardiac co-cultures. After 15 days in LGSF conditions, CMs exhibit elongated morphology, organized sarcomeres, polarized connexin-43, mitochondrial redistribution, and sarcoplasmic reticulum (SR) development, all closely resembling features of adult cells. These structural hallmarks were paralleled by enhanced Ca2+ handling, with increased SR contribution and reduced spontaneous activity, indicative of a mature ECC phenotype. When co-cultured with sympathetic neurons (SN), CMs established anatomically distinct neuro-cardiac junctions. Notably, nicotine stimulation triggered spatially restricted, reversible increases in CM Ca2+ transients, confined to varicosity-contacted cells. Pharmacological analysis revealed subtype-specific roles for β1- and β2-adrenergic receptors, and uncovered evidence of functional crosstalk between them. Our study defines a reproducible culture framework that advances CM maturation and enables the high-resolution interrogation of synaptic-like sympathetic modulation. This approach opens new avenues for mechanistic studies and drug testing in developmentally relevant neuro-cardiac systems.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 18","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prenatal Choline Attenuates the Elevated Adiposity and Glucose Intolerance Caused by Prenatal Alcohol Exposure. 产前胆碱可减轻产前酒精暴露引起的肥胖和葡萄糖耐受不良升高。

IF 5.2 2区生物学

Cells Pub Date : 2025-09-12 DOI: 10.3390/cells14181429

Susan M Smith, Carolyn A Munson, George R Flentke, Sandra M Mooney

{"title":"Prenatal Choline Attenuates the Elevated Adiposity and Glucose Intolerance Caused by Prenatal Alcohol Exposure.","authors":"Susan M Smith, Carolyn A Munson, George R Flentke, Sandra M Mooney","doi":"10.3390/cells14181429","DOIUrl":"10.3390/cells14181429","url":null,"abstract":"Prenatal alcohol exposure (PAE) causes neurobehavioral deficits and metabolic syndrome in later life. Prenatal choline supplementation (PCS) improves those behavioral deficits. Here we test whether PCS also ameliorates the attendant metabolic syndrome, using an established mouse model that mirrors aspects of alcohol-related neurodevelopmental disorders. Pregnant dams were exposed to alcohol (3 g/kg) from gestational days 8.5-17.5; some dams received additional choline (175% of requirement) by a daily injection. Offspring were followed through to the age of 86 wks with respect to their body composition and glucose tolerance. We found that PAE affected these outcomes in a sex-dependent manner. Male PAE offspring exhibited an increased fat mass, liver enlargement, elevated fasting glucose, and glucose intolerance. Female PAE offspring exhibited an increased fat mass, but the glucose tolerance and fasting values were unaffected. Regardless of sex, PCS attenuated all these metabolic measures. PCS was shown previously to elevate methyl-related choline metabolites and improve fetal growth, suggesting that it acts by attenuating the in utero stressors that otherwise program the fetus for metabolic syndrome in later life. Importantly, PCS also improved the adiposity, fasting glucose, and glucose tolerance in control offspring consuming the fixed-nutrient AIN-93G diet, suggesting that its choline content (1 g/kg) may be inadequate for optimal rodent health.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 18","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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