{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T11:53:01Z","timestamp":1768823581081,"version":"3.49.0"},"reference-count":74,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,19]],"date-time":"2022-06-19T00:00:00Z","timestamp":1655596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology, Taiwan","award":["MOST 104-2321-B-019-005-MY3"],"award-info":[{"award-number":["MOST 104-2321-B-019-005-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The common carp is a hypoxia-tolerant fish, and the understanding of its ability to live in low-oxygen environments has been applied to human health issues such as cancer and neuron degeneration. Here, we investigated differential gene expression changes during hypoxia in five common carp organs including the brain, the gill, the head kidney, the liver, and the intestine. Based on RNA sequencing, gene expression changes under hypoxic conditions were detected in over 1800 genes in common carp. The analysis of these genes further revealed that all five organs had high expression-specific properties. According to the results of the GO and KEGG, the pathways involved in the adaptation to hypoxia provided information on responses specific to each organ in low oxygen, such as glucose metabolism and energy usage, cholesterol synthesis, cell cycle, circadian rhythm, and dopamine activation. DisGeNET analysis showed that some human diseases such as cancer, diabetes, epilepsy, metabolism diseases, and social ability disorders were related to hypoxia-regulated genes. Our results suggested that common carp undergo various gene regulations in different organs under hypoxic conditions, and integrative bioinformatics may provide some potential targets for advancing disease research.<\/jats:p>","DOI":"10.3390\/genes13061096","type":"journal-article","created":{"date-parts":[[2022,6,19]],"date-time":"2022-06-19T10:14:52Z","timestamp":1655633692000},"page":"1096","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparative Transcriptome Analysis of Organ-Specific Adaptive Responses to Hypoxia Provides Insights to Human Diseases"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7643-9218","authenticated-orcid":false,"given":"Kuo-Sheng","family":"Hung","sequence":"first","affiliation":[{"name":"Center for Precision Medicine and Genomics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiow-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6873-6434","authenticated-orcid":false,"given":"Pang-Hung","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo-An","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan"},{"name":"Biotools Co., Ltd., New Taipei City 221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin-Hua","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cing-Han","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Information Engineering, National Taipei University of Technology, Taipei 114, Taiwan"},{"name":"Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung 202, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2869-4169","authenticated-orcid":false,"given":"Tun-Wen","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Information Engineering, National Taipei University of Technology, Taipei 114, Taiwan"},{"name":"Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung 202, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Shyong","family":"Tzou","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin-Yu","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan"},{"name":"Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan 244, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shi, R., Liao, C., and Zhang, Q. (2021). Hypoxia-Driven Effects in Cancer: Characterization, Mechanisms, and Therapeutic Implications. Cells, 10.","DOI":"10.3390\/cells10030678"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Manuelli, V., Pecorari, C., Filomeni, G., and Zito, E. (2021). Regulation of redox signaling in HIF-1-dependent tumor angiogenesis. FEBS J.","DOI":"10.1111\/febs.16110"},{"key":"ref_3","first-page":"002","article-title":"Cancer and the cellular response to hypoxia","volume":"1","author":"Adamaki","year":"2012","journal-title":"Pediatr. Therapeut. S"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1016\/j.stemcr.2017.05.001","article-title":"Hypoxia Epigenetically Confers Astrocytic Differentiation Potential on Human Pluripotent Cell-Derived Neural Precursor Cells","volume":"8","author":"Yasui","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1038\/cdd.2011.44","article-title":"Integration of CNS survival and differentiation by HIF2alpha","volume":"18","author":"Ko","year":"2011","journal-title":"Cell Death Differ."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1242\/jeb.205.6.759","article-title":"Cardiorespiratory responses of the common carp (Cyprinus carpio) to severe hypoxia at three acclimation temperatures","volume":"205","author":"Stecyk","year":"2002","journal-title":"J. Exp. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1242\/jeb.066183","article-title":"Differential effects of chronic hypoxia and feed restriction on the expression of leptin and its receptor, food intake regulation and the endocrine stress response in common carp","volume":"215","author":"Bernier","year":"2012","journal-title":"J. Exp. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1111\/jfb.12877","article-title":"Differential responses to environmental challenge by common carp Cyprinus carpio highlight the importance of coping style in integrative physiology","volume":"88","author":"Rey","year":"2016","journal-title":"J. Fish Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/tox.22217","article-title":"Cellular and molecular hypoxic response in common carp (Cyprinus carpio) exposed to linear alkylbenzene sulfonate at sublethal concentrations","volume":"32","author":"Tasaki","year":"2017","journal-title":"Environ. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1038\/ng.3098","article-title":"Genome sequence and genetic diversity of the common carp, Cyprinus carpio","volume":"46","author":"Xu","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkz114","article-title":"The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads","volume":"47","author":"Liao","year":"2019","journal-title":"Nucleic. Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/978-1-4939-3578-9_19","article-title":"It\u2019s DE-licious: A Recipe for Differential Expression Analyses of RNA-seq Experiments Using Quasi-Likelihood Methods in edgeR","volume":"1418","author":"Lun","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wei, Q., Khan, I.K., Ding, Z., Yerneni, S., and Kihara, D. (2017). NaviGO: Interactive tool for visualization and functional similarity and coherence analysis with gene ontology. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1600-5"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/10934520903425780","article-title":"Oxidative stress induced on Cyprinus carpio by contaminants present in the water and sediment of Madin Reservoir","volume":"45","year":"2010","journal-title":"J. Environ. Sci. Health A Tox Hazard Subst. Environ. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0144-8609(82)90004-8","article-title":"Intensive carp Cyprinus carpio (L.) rearing in a farm pond in southern Germany and its effects on water quality","volume":"1","author":"Lukowicz","year":"1982","journal-title":"Aquac. Eng."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.gene.2014.07.034","article-title":"Duplication and differentiation of common carp (Cyprinus carpio) myoglobin genes revealed by BAC analysis","volume":"548","author":"Zhao","year":"2014","journal-title":"Gene"},{"key":"ref_20","first-page":"454","article-title":"Hypoxia-inducible factor (HIF)-3a2 serves as an endothelial cell fate executor during chronic hypoxia","volume":"21","author":"Jaskiewicz","year":"2022","journal-title":"EXCLI J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1007\/s12035-015-9637-9","article-title":"Effects of DDIT4 in Methamphetamine-Induced Autophagy and Apoptosis in Dopaminergic Neurons","volume":"54","author":"Li","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ecoenv.2017.02.042","article-title":"Reproductive toxicity of \u03b2-diketone antibiotic mixtures to zebrafish (Danio rerio)","volume":"141","author":"Wang","year":"2017","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.molcel.2017.06.002","article-title":"The EGLN-HIF O2-Sensing System: Multiple Inputs and Feedbacks","volume":"66","author":"Ivan","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S1546-5098(08)00010-1","article-title":"Chapter 10 Metabolic and Molecular Responses of Fish to Hypoxia","volume":"Volume 27","author":"Richards","year":"2009","journal-title":"Fish Physiology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R1079","DOI":"10.1152\/ajpregu.00626.2004","article-title":"Oxygen-dependent gene expression in fishes","volume":"288","author":"Nikinmaa","year":"2005","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1007\/s10695-021-00989-8","article-title":"Effects of acute hypoxia and reoxygenation on oxygen sensors, respiratory metabolism, oxidative stress, and apoptosis in hybrid yellow catfish \u201cHuangyou-1\u201d","volume":"47","author":"Pei","year":"2021","journal-title":"Fish Physiol. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1046\/j.1432-1033.2003.03678.x","article-title":"Isolation, characterization and expression analysis of a hypoxia-responsive glucose transporter gene from the grass carp, Ctenopharyngodon idellus","volume":"270","author":"Zhang","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s10863-007-9080-3","article-title":"Hypoxia, glucose metabolism and the Warburg\u2019s effect","volume":"39","author":"Bartrons","year":"2007","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e190","DOI":"10.1038\/oncsis.2015.50","article-title":"Hypoxia and metabolic adaptation of cancer cells","volume":"5","author":"Eales","year":"2016","journal-title":"Oncogenesis"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.2147\/OTT.S290284","article-title":"The ALDOA Metabolism Pathway as a Potential Target for Regulation of Prostate Cancer Proliferation","volume":"14","author":"Kuang","year":"2021","journal-title":"Onco Targets Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.18632\/aging.204010","article-title":"The role of fructose 1,6-bisphosphate-mediated glycolysis\/gluconeogenesis genes in cancer prognosis","volume":"14","author":"Li","year":"2022","journal-title":"Aging"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1093\/abbs\/gmt148","article-title":"Hypoxia and cancer cell metabolism","volume":"46","author":"Huang","year":"2014","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1007\/s00360-013-0762-3","article-title":"Strategies for hypoxia adaptation in fish species: A review","volume":"183","author":"Zhu","year":"2013","journal-title":"J. Comp. Physiol. B"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"112563","DOI":"10.1016\/j.biopha.2021.112563","article-title":"AMPK signaling in diabetes mellitus, insulin resistance and diabetic complications: A pre-clinical and clinical investigation","volume":"146","author":"Entezari","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.7150\/ijbs.27173","article-title":"The PI3K\/AKT pathway in obesity and type 2 diabetes","volume":"14","author":"Huang","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Van Den Thillart, G., Addink, A., Balm, P., Nieveen, M., Van Ginneken, V.J., and Van Caubergh, P. (1997). Influence of Hypoxia Exposure on the Energy Metabolism of Common Carp (Cyprinus carpio, L.), Brill.","DOI":"10.1163\/156854298X00228"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/BF02337889","article-title":"Substrate mobilization and hormonal changes in rainbow trout (Oncorhynchus mykiss, L.) and common carp (Cyprinus carpio, L.) during deep hypoxia and subsequent recovery","volume":"166","author":"Vianen","year":"1996","journal-title":"J. Comp. Physiol. B"},{"key":"ref_38","first-page":"113","article-title":"The effects of cadmium on levels of glucose in serum and glycogen reserves in the liver and muscle tissues of Cyprinus carpio (L., 1758)","volume":"29","author":"Cicik","year":"2005","journal-title":"Turk. J. Vet. Anim. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1006\/gcen.2001.7725","article-title":"Hematological effects of high dose of cortisol on the carp (Cyprinus carpio L.): Cortisol effect on the carp blood","volume":"125","author":"Wojtaszek","year":"2002","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/0300-9629(94)90219-4","article-title":"Energy status and free fatty acid patterns in tissues of common carp (Cyprinus carpio, L.) and rainbow trout (Oncorhynchus mykiss, L.) during severe oxygen restriction","volume":"109","author":"Bakker","year":"1994","journal-title":"Comparative Biochem. Physiol. Part A Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1163\/156854201750210823","article-title":"Plasma lactate and stress hormones in common carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) during stepwise decreasing oxygen levels","volume":"51","author":"Vianen","year":"2001","journal-title":"Neth. J. Zool."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1111\/j.1095-8649.2000.tb00478.x","article-title":"Metabolic adjustments in the common carp during prolonged hypoxia","volume":"57","author":"Zhou","year":"2000","journal-title":"J. Fish Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.cbpa.2014.09.017","article-title":"The combined effect of hypoxia and nutritional status on metabolic and ionoregulatory responses of common carp (Cyprinus carpio)","volume":"179","author":"Moyson","year":"2015","journal-title":"Comp. Biochem. Physiol. Part A Mol. Integr. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1007\/s10695-020-00887-5","article-title":"Hypoxia-mediated inhibition of cholesterol synthesis leads to disruption of nocturnal sex steroidogenesis in the gonad of koi carp, Cyprinus carpio","volume":"46","author":"Bera","year":"2020","journal-title":"Fish Physiol. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1042\/CS20201394","article-title":"Cholesterol metabolism: A new molecular switch to control inflammation","volume":"135","author":"Cardoso","year":"2021","journal-title":"Clin. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e0307321","DOI":"10.1128\/mbio.03073-21","article-title":"Coxiella burnetii Sterol-Modifying Protein Stmp1 Regulates Cholesterol in the Intracellular Niche","volume":"13","author":"Clemente","year":"2022","journal-title":"mBio"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1086\/673180","article-title":"Interspecific differences in hypoxia-induced gill remodeling in carp","volume":"86","author":"Dhillon","year":"2013","journal-title":"Physiol. Biochem. Zool."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.resp.2012.07.012","article-title":"New insights into the plasticity of gill structure","volume":"184","author":"Nilsson","year":"2012","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1128\/MCB.23.1.359-369.2003","article-title":"Hypoxia-inducible factor 1alpha is essential for cell cycle arrest during hypoxia","volume":"23","author":"Goda","year":"2003","journal-title":"Mol. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1046\/j.1356-9597.2001.00512.x","article-title":"Hypoxia-inducible factor-1alpha induces cell cycle arrest of endothelial cells","volume":"7","author":"Iida","year":"2002","journal-title":"Genes. Cells"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Druker, J., Wilson, J.W., Child, F., Shakir, D., Fasanya, T., and Rocha, S. (2021). Role of Hypoxia in the Control of the Cell Cycle. Int J Mol Sci., 22.","DOI":"10.3390\/ijms22094874"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/S0002-9440(10)63483-9","article-title":"Hypoxia-induced gene expression in human macrophages: Implications for ischemic tissues and hypoxia-regulated gene therapy","volume":"163","author":"Burke","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.3346\/jkms.2015.30.10.1388","article-title":"HIF-1alpha Upregulation due to Depletion of the Free Ubiquitin Pool","volume":"30","author":"Kim","year":"2015","journal-title":"J. Korean Med. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1007\/s10646-011-0702-5","article-title":"Hypoxia-induced oxidative DNA damage links with higher level biological effects including specific growth rate in common carp, Cyprinus carpio L.","volume":"20","author":"Mustafa","year":"2011","journal-title":"Ecotoxicology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"448","DOI":"10.3389\/fgene.2018.00448","article-title":"Genetic Mapping of Head Size Related Traits in Common Carp (Cyprinus carpio)","volume":"9","author":"Chen","year":"2018","journal-title":"Front. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"173758","DOI":"10.1016\/j.ejphar.2020.173758","article-title":"FoxO1 signaling as a therapeutic target for type 2 diabetes and obesity","volume":"891","author":"Benchoula","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Gabryelska, A., Sochal, M., Turkiewicz, S., and Bialasiewicz, P. (2020). Relationship between HIF-1 and Circadian Clock Proteins in Obstructive Sleep Apnea Patients-Preliminary Study. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051599"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"100764","DOI":"10.1016\/j.yfrne.2019.100764","article-title":"The role of sleep deprivation and circadian rhythm disruption as risk factors of Alzheimer\u2019s disease","volume":"54","author":"Wu","year":"2019","journal-title":"Front. Neuroendocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/JAD-190848","article-title":"Is Alzheimer\u2019s Disease a Liver Disease of the Brain?","volume":"75","author":"Bassendine","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Peng, X., Fan, R., Xie, L., Shi, X., Dong, K., Zhang, S., Tao, J., Xu, W., Ma, D., and Chen, J. (2022). A Growing Link between Circadian Rhythms, Type 2 Diabetes Mellitus and Alzheimer\u2019s Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010504"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0300-9629(95)02127-2","article-title":"Neurotransmitter levels and energy status in brain of fish species with and without the survival strategy of metabolic depression","volume":"114","author":"Nieveen","year":"1996","journal-title":"Comp. Biochem. Physiol. Part A Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.cbpa.2012.12.020","article-title":"Cardiac K(ATP) channel alterations associated with acclimation to hypoxia in goldfish (Carassius auratus L.)","volume":"164","author":"Cameron","year":"2013","journal-title":"Comp. Biochem. Physiol. A Mol. Integr. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0361-9230(01)00604-9","article-title":"Role of pH on the calcium ion dependence of the nitric oxide synthase in the carp brain","volume":"56","author":"Conte","year":"2001","journal-title":"Brain Res. Bull"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8738","DOI":"10.1007\/s12035-018-1017-9","article-title":"Hypoxia-Induced Neuroinflammation and Learning-Memory Impairments in Adult Zebrafish Are Suppressed by Glucosamine","volume":"55","author":"Lee","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4570","DOI":"10.1038\/s41380-020-00997-9","article-title":"Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders","volume":"26","author":"Delhaye","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1242\/jeb.200.2.411","article-title":"Contrasting strategies for anoxic brain survival--glycolysis up or down","volume":"200","author":"Lutz","year":"1997","journal-title":"J. Exp. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1007\/s11306-013-0540-y","article-title":"1H-NMR study of the metabolome of a moderately hypoxia-tolerant fish, the common carp (Cyprinus carpio)","volume":"9","author":"Lardon","year":"2013","journal-title":"Metabolomics"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s10695-019-00708-4","article-title":"Dietary GABA enhances hypoxia tolerance of a bottom-dwelling carp, Cirrhinus mrigala by modulating HIF-1alpha, thyroid hormones and metabolic responses","volume":"46","author":"Varghese","year":"2020","journal-title":"Fish Physiol. Biochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ygcen.2016.11.009","article-title":"Zymosan-induced immune challenge modifies the stress response of hypoxic air-breathing fish (Anabas testudineus Bloch): Evidence for reversed patterns of cortisol and thyroid hormone interaction, differential ion transporter functions and non-specific immune response","volume":"251","author":"Simi","year":"2017","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1179069517733732","DOI":"10.1177\/1179069517733732","article-title":"Hypoxia Stress Modifies Na(+)\/K(+)-ATPase, H(+)\/K(+)-ATPase, [Formula: See text], and nkaalpha1 Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish","volume":"11","author":"Peter","year":"2017","journal-title":"J. Exp. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3389\/fncel.2018.00167","article-title":"Cortical GABAergic Interneuron\/Progenitor Transplantation as a Novel Therapy for Intractable Epilepsy","volume":"12","author":"Zhu","year":"2018","journal-title":"Front. Cell Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"106935","DOI":"10.1016\/j.yebeh.2020.106935","article-title":"GABAergic interneurons in epilepsy: More than a simple change in inhibition","volume":"121","author":"Calcagnotto","year":"2021","journal-title":"Epilepsy Behav."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.2174\/092986711797200426","article-title":"Hypoxia inducible factor-1 as a target for neurodegenerative diseases","volume":"18","author":"Zhang","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Belikova, M.V., Kolesnikova, E.E., and Serebrovskaya, T.V. (2012). Intermittent hypoxia and experimental Parkinson\u2019s disease. Intermittent Hypoxia and Human Diseases, Springer.","DOI":"10.1007\/978-1-4471-2906-6_12"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/6\/1096\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:35:13Z","timestamp":1760139313000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/6\/1096"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,19]]},"references-count":74,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["genes13061096"],"URL":"https:\/\/doi.org\/10.3390\/genes13061096","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,19]]}}}