Lab Animal最新文献_第7页

Murine model of minimally invasive nasal depot (MIND) technique for central nervous system delivery of blood–brain barrier-impermeant therapeutics 用于中枢神经系统输送血脑屏障渗透疗法药物的微创鼻腔药库（MIND）小鼠模型

IF 5.9 3区农林科学

Lab Animal Pub Date : 2024-11-15 DOI: 10.1038/s41684-024-01460-w

Andy J. Chua, Valentina Di Francesco, Anisha D’Souza, Mansoor Amiji, Benjamin S. Bleier

{"title":"Murine model of minimally invasive nasal depot (MIND) technique for central nervous system delivery of blood–brain barrier-impermeant therapeutics","authors":"Andy J. Chua, Valentina Di Francesco, Anisha D’Souza, Mansoor Amiji, Benjamin S. Bleier","doi":"10.1038/s41684-024-01460-w","DOIUrl":"10.1038/s41684-024-01460-w","url":null,"abstract":"The blood–brain barrier (BBB) poses a substantial obstacle to the successful delivery of therapeutics to the central nervous system (CNS). The transnasal route has been extensively explored, but success rates have been modest due to challenges related to the precise anatomical placement of drugs, the small volumes that the olfactory cleft can accommodate and short drug residence times due to mucociliary clearance. Here, to address these issues, we have developed a surgical technique known as the minimally invasive nasal depot (MIND), which allows the accurate placement of depot drugs into the submucosal space of the olfactory epithelium of rats. This technique exploits the unique anatomy of the olfactory apparatus to enable transnasal delivery of drugs into the CNS, bypassing the BBB. In our rat model, a bony window is created in the animal snout to expose the submucosal space. Using the MIND technique, we have successfully delivered oligonucleotides to the CNS in Sprague-Dawley and Long-Evans rats, leading to an upregulation of brain-derived neurotrophic factor in the substantia nigra and hippocampus. In this Protocol, we describe the procedural steps for MIND. This procedure takes about 45 min and can be performed by researchers with basic surgical skills. We additionally describe modifications to perform MIND in mice, which are anatomically smaller. The MIND procedure represents a unique platform that can be used to overcome the limitations posed by the BBB. This technique can potentially expand the therapeutic toolkit in the treatment of neurological diseases. This Protocol describes a minimally invasive technique for central nervous system drug delivery in rodents. The procedure allows the use of the transnasal route to deliver blood–brain barrier-impermeant drugs.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"53 12","pages":"363-375"},"PeriodicalIF":5.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and evaluation of an autism pig model 自闭症猪模型的开发与评估

IF 5.9 3区农林科学

Lab Animal Pub Date : 2024-11-12 DOI: 10.1038/s41684-024-01475-3

Shuai Qiu, Jingyan Jia, Benlei Xu, Nan Wu, Huaqiang Cao, Shuangyi Xie, Jialong Cui, Ji Ma, Yi-Hsuan Pan, Xiao-Bing Yuan

{"title":"Development and evaluation of an autism pig model","authors":"Shuai Qiu, Jingyan Jia, Benlei Xu, Nan Wu, Huaqiang Cao, Shuangyi Xie, Jialong Cui, Ji Ma, Yi-Hsuan Pan, Xiao-Bing Yuan","doi":"10.1038/s41684-024-01475-3","DOIUrl":"10.1038/s41684-024-01475-3","url":null,"abstract":"Developing cost-effective and disease-relevant animal models is essential for advancing biomedical research into human disorders. Here we investigate the feasibility of a pig model for autism spectrum disorder (ASD) using embryonic exposure to valproic acid (VPA), an antiepileptic drug known to increase ASD risk. We established experimental paradigms to assess the behavioral characteristics of these pig models. Administration of VPA to Bama miniature pigs (Sus scrofa domestica) during critical embryonic stages resulted in abnormal gait, increased anxiety levels, reduced learning capabilities and altered social patterns, while largely preserving social preference of treated piglets. Notably, we detected significant neuroanatomical changes in cortical regions associated with ASD in the VPA-treated pigs, including cortical malformation, increased neuronal soma size, decreased dendritic complexity and reduced dendritic spine maturation. Transcriptome analysis of the prefrontal cortex of VPA-treated pigs further revealed substantial alterations in the expression of genes linked to ASD, especially genes of the dopamine signaling pathway, highlighting the model’s relevance and potential for shedding light on ASD’s underlying neuropathological and molecular mechanisms. These findings suggest that pig models could serve as a promising alternative to traditional rodent models and provide a more ethical substitute for the use of primates in translational research on neurodevelopmental disorders. This study describes a new pig model of autism induced by embryonic exposure to valproic acid. The pig model displays behavioral alterations, abnormal gait and increased anxiety, which recapitulate key features of autism.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"53 12","pages":"376-386"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01475-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A facility for laboratory mice with a natural microbiome at Charité – Universitätsmedizin Berlin 柏林夏里特大学自然微生物组实验小鼠设施

IF 5.9 3区农林科学

Lab Animal Pub Date : 2024-11-12 DOI: 10.1038/s41684-024-01474-4

Natascha Drude, Stefan Nagel-Riedasch, Stephan P. Rosshart, Andreas Diefenbach, The “Charité 3R Wildling Mouse Model in Health and Disease (C3R Wildling HeaD)” consortium, Stefan Jordan

引用次数: 0

Hydroxyapatite nanoparticles neurotoxicity 羟基磷灰石纳米颗粒的神经毒性

IF 5.9 3区农林科学

Lab Animal Pub Date : 2024-10-29 DOI: 10.1038/s41684-024-01467-3

Jorge Ferreira

引用次数: 0

Midkine links aging and breast cancer Midkine 将衰老与乳腺癌联系起来

IF 5.9 3区农林科学

Lab Animal Pub Date : 2024-10-29 DOI: 10.1038/s41684-024-01470-8

Alexandra Le Bras

引用次数: 0

Pregnancy confers immune protection against influenza A virus infection 妊娠对甲型流感病毒感染具有免疫保护作用