{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:22:58Z","timestamp":1760145778396,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"publisher","award":["JP 22K07346","21J40098JP","24K10677","LSI 23103","JPMJMS2297"],"award-info":[{"award-number":["JP 22K07346","21J40098JP","24K10677","LSI 23103","JPMJMS2297"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Life Science Innovation Center, University of Fukui,","award":["JP 22K07346","21J40098JP","24K10677","LSI 23103","JPMJMS2297"],"award-info":[{"award-number":["JP 22K07346","21J40098JP","24K10677","LSI 23103","JPMJMS2297"]}]},{"name":"Initiative for Realizing Diversity in the Research Environment, MEXT","award":["JP 22K07346","21J40098JP","24K10677","LSI 23103","JPMJMS2297"],"award-info":[{"award-number":["JP 22K07346","21J40098JP","24K10677","LSI 23103","JPMJMS2297"]}]},{"name":"Tokai Bussan Co., Ltd.","award":["JP 22K07346","21J40098JP","24K10677","LSI 23103","JPMJMS2297"],"award-info":[{"award-number":["JP 22K07346","21J40098JP","24K10677","LSI 23103","JPMJMS2297"]}]},{"name":"Japan Science and Technology Agency, JST","award":["JP 22K07346","21J40098JP","24K10677","LSI 23103","JPMJMS2297"],"award-info":[{"award-number":["JP 22K07346","21J40098JP","24K10677","LSI 23103","JPMJMS2297"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Corticosterone, an end product of the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis, is a crucial stress hormone. A dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders, such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.<\/jats:p>","DOI":"10.3390\/nu16172821","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T12:53:19Z","timestamp":1724417599000},"page":"2821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral Supplementation of L-Carnosine Attenuates Acute-Stress-Induced Corticosterone Release and Mitigates Anxiety in CD157 Knockout Mice"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3671-0728","authenticated-orcid":false,"given":"Takahiro","family":"Tsuji","sequence":"first","affiliation":[{"name":"Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan"},{"name":"Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan"},{"name":"Life Science Innovation Center, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazumi","family":"Furuhara","sequence":"additional","affiliation":[{"name":"Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erchu","family":"Guo","sequence":"additional","affiliation":[{"name":"Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan"},{"name":"Departments of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yijing","family":"Wu","sequence":"additional","affiliation":[{"name":"Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan"},{"name":"School of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhong","sequence":"additional","affiliation":[{"name":"Physiological Department, Guangxi University of Chinese Medicine, Nanning 530011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1779-0606","authenticated-orcid":false,"given":"Haruhiro","family":"Higashida","sequence":"additional","affiliation":[{"name":"Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1326-4649","authenticated-orcid":false,"given":"Yasuhiko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiharu","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan"},{"name":"Department of Socioneurosciences, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Kanazawa Campus, Kanazawa 920-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"588","DOI":"10.2174\/0113895575262104230928042150","article-title":"Cortisol as a Target for Treating Mental Disorders: A Promising Avenue for Therapy","volume":"24","author":"Patel","year":"2024","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13478","DOI":"10.1111\/asj.13478","article-title":"Nutritional interventions for promoting stress resilience: Recent progress using psychosocial stress models of rodents","volume":"91","author":"Toyoda","year":"2020","journal-title":"Anim. Sci. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1073\/pnas.85.9.3175","article-title":"Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain","volume":"85","author":"Kohen","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0003-9861(60)90059-X","article-title":"The significance of carnosine and anserine in striated skeletal muscle","volume":"89","author":"Davey","year":"1960","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1161\/STROKEAHA.114.005183","article-title":"Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage","volume":"45","author":"Baek","year":"2014","journal-title":"Stroke"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3233\/JAD-150767","article-title":"Effect of Anserine\/Carnosine Supplementation on Verbal Episodic Memory in Elderly People","volume":"50","author":"Hisatsune","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s00726-021-02960-6","article-title":"Effect of L-Carnosine in children with autism spectrum disorders: A systematic review and meta-analysis of randomised controlled trials","volume":"53","author":"Abraham","year":"2021","journal-title":"Amino Acids"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.psychres.2018.02.012","article-title":"L-carnosine as an add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: A double-blind, randomized placebo-controlled trial","volume":"262","author":"Ghajar","year":"2018","journal-title":"Psychiatry Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e01074","DOI":"10.1002\/prp2.1074","article-title":"Cognitive and negative symptoms in schizophrenia with L-Carnosine adjuvant therapy\u2014A randomized double-blind placebo-controlled study","volume":"11","author":"Tharoor","year":"2023","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"334","DOI":"10.14336\/AD.2017.0809","article-title":"Anserine\/Carnosine Supplementation Preserves Blood Flow in the Prefrontal Brain of Elderly People Carrying APOE e4","volume":"9","author":"Ding","year":"2018","journal-title":"Aging Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Masuoka, N., Yoshimine, C., Hori, M., Tanaka, M., Asada, T., Abe, K., and Hisatsune, T. (2019). Effects of Anserine\/Carnosine Supplementation on Mild Cognitive Impairment with APOE4. Nutrients, 11.","DOI":"10.3390\/nu11071626"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1089\/cap.2017.0157","article-title":"l-Carnosine as Adjunctive Therapy in Children and Adolescents with Attention-Deficit\/Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial","volume":"28","author":"Ghajar","year":"2018","journal-title":"J. Child. Adolesc. Psychopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"69","DOI":"10.5539\/gjhs.v5n3p69","article-title":"Carnosine treatment for gulf war illness: A randomized controlled trial","volume":"5","author":"Baraniuk","year":"2013","journal-title":"Glob. J. Health Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Li, Y.F., He, R.R., Tsoi, B., Li, X.D., Li, W.X., Abe, K., and Kurihara, H. (2012). Anti-stress effects of carnosine on restraint-evoked immunocompromise in mice through spleen lymphocyte number maintenance. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033190"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1254\/jphs.11131FP","article-title":"Carnosine ameliorates stress-induced glucose metabolism disorder in restrained mice","volume":"117","author":"Tsoi","year":"2011","journal-title":"J. Pharmacol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5325","DOI":"10.1073\/pnas.91.12.5325","article-title":"BST-1, a surface molecule of bone marrow stromal cell lines that facilitates pre-B-cell growth","volume":"91","author":"Kaisho","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1152\/physrev.00035.2007","article-title":"Evolution and function of the ADP ribosyl cyclase\/CD38 gene family in physiology and pathology","volume":"88","author":"Malavasi","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_18","first-page":"235","article-title":"BST-1\/CD157 regulates the humoral immune responses in vivo","volume":"75","author":"Ishihara","year":"2000","journal-title":"Chem. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yokoyama, S. (2023). Genetic polymorphisms of bone marrow stromal cell antigen-1 (BST-1\/CD157): Implications for immune\/inflammatory dysfunction in neuropsychiatric disorders. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1197265"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3390\/brainsci5020188","article-title":"Association Study between the CD157\/BST1 Gene and Autism Spectrum Disorders in a Japanese Population","volume":"5","author":"Yokoyama","year":"2015","journal-title":"Brain Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/08039488.2017.1410570","article-title":"A study of single nucleotide polymorphisms in CD157, AIM2 and JARID2 genes in Han Chinese children with autism spectrum disorder","volume":"72","author":"Mo","year":"2018","journal-title":"Nord. J. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lopatina, O., Yoshihara, T., Nishimura, T., Zhong, J., Akther, S., Fakhrul, A.A., Liang, M., Higashida, C., Sumi, K., and Furuhara, K. (2014). Anxiety- and depression-like behavior in mice lacking the CD157\/BST1 gene, a risk factor for Parkinson\u2019s disease. Front. Behav. Neurosci., 8.","DOI":"10.3389\/fnbeh.2014.00133"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3390\/brainsci5010003","article-title":"Lipo-oxytocin-1, a Novel Oxytocin Analog Conjugated with Two Palmitoyl Groups, Has Long-Lasting Effects on Anxiety-Related Behavior and Social Avoidance in CD157 Knockout Mice","volume":"5","author":"Mizuno","year":"2015","journal-title":"Brain Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kasai, S., Yoshihara, T., Lopatina, O., Ishihara, K., and Higashida, H. (2017). Selegiline Ameliorates Depression-Like Behavior in Mice Lacking the CD157\/BST1 Gene, a Risk Factor for Parkinson's Disease. Front. Behav. Neurosci., 11.","DOI":"10.3389\/fnbeh.2017.00075"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Tsuji, T., Furuhara, K., Gerasimenko, M., Shabalova, A., Cherepanov, S.M., Minami, K., Higashida, H., and Tsuji, C. (2022). Oral Supplementation with L-Carnosine Attenuates Social Recognition Deficits in CD157KO Mice via Oxytocin Release. Nutrients, 14.","DOI":"10.3390\/nu14040803"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1046\/j.1365-2826.1999.00403.x","article-title":"Emotional stress triggers intrahypothalamic but not peripheral release of oxytocin in male rats","volume":"11","author":"Engelmann","year":"1999","journal-title":"J. Neuroendocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00441-018-2866-2","article-title":"The interplay between oxytocin and the CRF system: Regulation of the stress response","volume":"375","author":"Winter","year":"2019","journal-title":"Cell Tissue Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1210\/endo.138.7.5255","article-title":"Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats","volume":"138","author":"Windle","year":"1997","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.psyneuen.2005.04.002","article-title":"Intranasal oxytocin administration attenuates the ACTH stress response in monkeys","volume":"30","author":"Parker","year":"2005","journal-title":"Psychoneuroendocrinology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1523\/JNEUROSCI.3432-03.2004","article-title":"Oxytocin attenuates stress-induced c-fos mRNA expression in specific forebrain regions associated with modulation of hypothalamo-pituitary-adrenal activity","volume":"24","author":"Windle","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4687","DOI":"10.1523\/JNEUROSCI.0342-09.2009","article-title":"Oxytocin Influence on NTS: Beyond Homeostatic Regulation","volume":"29","author":"Karelina","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s10567-011-0097-0","article-title":"Anxiety disorders in children and adolescents with autistic spectrum disorders: A meta-analysis","volume":"14","author":"Bogels","year":"2011","journal-title":"Clin. Child. Fam. Psychol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1007\/s10826-017-0687-7","article-title":"Anxiety Levels in Children with Autism Spectrum Disorder: A Meta-Analysis","volume":"26","author":"Heeman","year":"2017","journal-title":"J. Child Fam. Stud."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1017\/S0033291718002283","article-title":"Anxiety and depression in adults with autism spectrum disorder: A systematic review and meta-analysis","volume":"49","author":"Hollocks","year":"2019","journal-title":"Psychol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.psyneuen.2014.07.015","article-title":"A review of rhythm and responsiveness of cortisol in individuals with autism spectrum disorders","volume":"49","author":"Taylor","year":"2014","journal-title":"Psychoneuroendocrinology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3343\/alm.2020.40.4.285","article-title":"Cortisol Measurements in Cushing's Syndrome: Immunoassay or Mass Spectrometry?","volume":"40","author":"Casals","year":"2020","journal-title":"Ann. Lab. Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/17\/2821\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:42:18Z","timestamp":1760110938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/17\/2821"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,23]]},"references-count":36,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["nu16172821"],"URL":"https:\/\/doi.org\/10.3390\/nu16172821","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2024,8,23]]}}}