{"date_published":"2023-04-27T00:00:00Z","publication_status":"published","issue":"9","department":[{"_id":"SiHi"},{"_id":"GaNo"}],"abstract":[{"text":"Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.","lang":"eng"}],"type":"journal_article","file":[{"content_type":"application/pdf","access_level":"open_access","creator":"dernst","file_name":"2023_Cell_Knaus.pdf","checksum":"47e94fbe19e86505b429cb7a5b503ce6","relation":"main_file","success":1,"file_id":"12889","file_size":15712841,"date_created":"2023-05-02T09:26:21Z","date_updated":"2023-05-02T09:26:21Z"}],"day":"27","article_processing_charge":"Yes (via OA deal)","month":"04","date_updated":"2024-02-07T08:03:32Z","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"title":"Large neutral amino acid levels tune perinatal neuronal excitability and survival","quality_controlled":"1","status":"public","related_material":{"record":[{"id":"13107","relation":"dissertation_contains","status":"public"}],"link":[{"url":"https://ista.ac.at/en/news/feed-them-or-lose-them/","relation":"press_release","description":"News on ISTA Website"}]},"oa_version":"Published Version","oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_created":"2023-04-05T08:15:40Z","publisher":"Elsevier","scopus_import":"1","citation":{"short":"L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A. Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N. Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25.","apa":"Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz, L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal excitability and survival. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">https://doi.org/10.1016/j.cell.2023.02.037</a>","ista":"Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA, Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.","chicago":"Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova, Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” <i>Cell</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">https://doi.org/10.1016/j.cell.2023.02.037</a>.","ama":"Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal neuronal excitability and survival. <i>Cell</i>. 2023;186(9):1950-1967.e25. doi:<a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">10.1016/j.cell.2023.02.037</a>","ieee":"L. Knaus <i>et al.</i>, “Large neutral amino acid levels tune perinatal neuronal excitability and survival,” <i>Cell</i>, vol. 186, no. 9. Elsevier, p. 1950–1967.e25, 2023.","mla":"Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” <i>Cell</i>, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25, doi:<a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">10.1016/j.cell.2023.02.037</a>."},"article_type":"original","ec_funded":1,"_id":"12802","language":[{"iso":"eng"}],"has_accepted_license":"1","author":[{"first_name":"Lisa","last_name":"Knaus","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa"},{"orcid":"0000-0003-1843-3173","last_name":"Basilico","first_name":"Bernadette","full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"last_name":"Malzl","first_name":"Daniel","full_name":"Malzl, Daniel"},{"last_name":"Gerykova Bujalkova","first_name":"Maria","full_name":"Gerykova Bujalkova, Maria"},{"last_name":"Smogavec","first_name":"Mateja","full_name":"Smogavec, Mateja"},{"full_name":"Schwarz, Lena A.","last_name":"Schwarz","first_name":"Lena A."},{"full_name":"Gorkiewicz, Sarah","id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f","last_name":"Gorkiewicz","first_name":"Sarah"},{"last_name":"Amberg","first_name":"Nicole","full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207"},{"orcid":"0000-0002-7462-0048","last_name":"Pauler","first_name":"Florian","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Knittl-Frank","first_name":"Christian","full_name":"Knittl-Frank, Christian"},{"last_name":"Tassinari","first_name":"Marianna","id":"7af593f1-d44a-11ed-bf94-a3646a6bb35e","full_name":"Tassinari, Marianna"},{"last_name":"Maulide","first_name":"Nuno","full_name":"Maulide, Nuno"},{"full_name":"Rülicke, Thomas","last_name":"Rülicke","first_name":"Thomas"},{"first_name":"Jörg","last_name":"Menche","full_name":"Menche, Jörg"},{"first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"},{"orcid":"0000-0002-7673-7178","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"publication":"Cell","page":"1950-1967.e25","doi":"10.1016/j.cell.2023.02.037","external_id":{"isi":["000991468700001"]},"publication_identifier":{"issn":["0092-8674"]},"keyword":["General Biochemistry","Genetics and Molecular Biology"],"isi":1,"file_date_updated":"2023-05-02T09:26:21Z","acknowledgement":"We thank A. Freeman and V. Voronin for technical assistance, S. Deixler, A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal colony. We thank L. Andersen and J. Sonntag, who were involved in generating the MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance with the proteomic analysis, as well as the ISTA electron microscopy and Imaging and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated using Biorender.com. This work was supported by the Austrian Science Fund (FWF, DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program (ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.","project":[{"call_identifier":"FWF","grant_number":"W1232-B24","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"},{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"}],"ddc":["570"],"intvolume":"       186","volume":186,"year":"2023","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"LifeSc"}]}