{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T06:42:16Z","timestamp":1769928136509,"version":"3.49.0"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>This article deals with Central Nervous System (CNS) disorders of marine mammals as putative neuropathology and neuropathogenesis models for their human and, to some extent, their animal \u201ccounterparts\u201d in a dual \u201cOne Health\u201d and \u201cTranslational Medicine\u201d perspective. Within this challenging context, special emphasis is placed upon Alzheimer\u2019s disease (AD), provided that AD-like pathological changes have been reported in the brain tissue of stranded cetacean specimens belonging to different Odontocete species. Further examples of potential comparative pathology interest are represented by viral infections and, in particular, by \u201cSubacute Sclerosing Panencephalitis\u201d (SSPE), a rare neurologic sequela in patients infected with Measles virus (MeV). Indeed, Cetacean morbillivirus (CeMV)-infected striped dolphins (Stenella coeruleoalba) may also develop a \u201cbrain-only\u201d form of CeMV infection, sharing neuropathological similarities with SSPE. Within this framework, the global threat of the A(H5N1) avian influenza virus is another major concern issue, with a severe meningoencephalitis occurring in affected pinnipeds and cetaceans, similarly to what is seen in human beings. Finally, the role of Brucella ceti-infected, neurobrucellosis-affected cetaceans as putative neuropathology and neuropathogenesis models for their human disease counterparts is also analyzed and discussed. Notwithstanding the above, much more work is needed before drawing the conclusion marine mammal CNS disorders mirror their human \u201canalogues\u201d.<\/jats:p>","DOI":"10.3390\/pathogens13080684","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T03:46:36Z","timestamp":1723607196000},"page":"684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Central Nervous System Disorders of Marine Mammals: Models for Human Disease?"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4592-1084","authenticated-orcid":false,"given":"Giovanni","family":"Di Guardo","sequence":"first","affiliation":[{"name":"Former Professor of General Pathology and Veterinary Pathophysiology, Veterinary Medical Faculty, University of Teramo, Localit\u00e0 Piano d\u2019Accio, 64100 Teramo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1177\/03009858231166663","article-title":"Central Nervous System Diseases of Cetaceans: A Conservation Challenge and a Comparative Pathology Opportunity","volume":"60","year":"2023","journal-title":"Vet. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wu, C.H., Pan, X.S., Su, L.Y., and Yang, S.Y. (2023). Plasma Neurofilament Light Chains as Blood-Based Biomarkers for Early Diagnosis of Canine Cognitive Dysfunction Syndrome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241813771"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jalz.2017.08.014","article-title":"Alzheimer\u2019s Disease in Humans and Other Animals: A Consequence of Postreproductive Life Span and Longevity Rather Than Aging","volume":"14","author":"Lovestone","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Sacchini, S., D\u00edaz-Delgado, J., Espinosa de Los Monteros, A., Paz, Y., Bernaldo de Quir\u00f3s, Y., Sierra, E., Arbelo, M., Herr\u00e1ez, P., and Fern\u00e1ndez, A. (2020). Amyloid-Beta Peptide and Phosphorylated Tau in the Frontopolar Cerebral Cortex and in the Cerebellum of Toothed Whales: Aging Versus Hypoxia. Biol. Open, 9.","DOI":"10.1242\/bio.054734"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1111\/ejn.15900","article-title":"Alzheimer\u2019s Disease-Like Neuropathology in Three Species of Oceanic Dolphin","volume":"57","author":"Vacher","year":"2023","journal-title":"Eur. J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Davis, D.A., Mondo, K., Stern, E., Annor, A.K., Murch, S.J., Coyne, T.M., Brand, L.E., Niemeyer, M.E., Sharp, S., and Bradley, W.G. (2019). Cyanobacterial Neurotoxin BMAA and Brain Pathology in Stranded Dolphins. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0213346"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Garamszegi, S.P., Brzostowicki, D.J., Coyne, T.M., Vontell, R.T., and Davis, D.A. (2024). TDP-43 and Alzheimer\u2019s Disease Pathology in the Brain of a Harbor Porpoise Exposed to the Cyanobacterial Toxin BMAA. Toxins, 16.","DOI":"10.3390\/toxins16010042"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/nature07761","article-title":"Cellular Prion Protein Mediates Impairment of Synaptic Plasticity by Amyloid-Beta Oligomers","volume":"457","author":"Gimbel","year":"2009","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.jalz.2017.12.002","article-title":"Alzheimer\u2019s Disease, Cellular Prion Protein, and Dolphins","volume":"14","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0378-1135(95)00016-4","article-title":"Evidence for Chronic Morbillivirus Infection in the Mediterranean Striped Dolphin (Stenella coeruleoalba)","volume":"44","author":"Domingo","year":"1995","journal-title":"Vet. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Di Guardo, G., and Mazzariol, S. (2016). Cetacean Morbillivirus-Associated Pathology: Knowns and Unknowns. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00112"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jcpa.2021.01.004","article-title":"Novel Presentation of DMV-Associated Encephalitis in a Long-Finned Pilot Whale (Globicephala melas)","volume":"183","author":"Wessels","year":"2021","journal-title":"J. Comp. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3354\/dao02387","article-title":"Post-Epizootic Chronic Dolphin Morbillivirus Infection in Mediterranean Striped Dolphins Stenella coeruleoalba","volume":"96","author":"Soto","year":"2011","journal-title":"Dis. Aquat. Organ."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"495","DOI":"10.4149\/av_2017_414","article-title":"Neuronal and Astrocytic Involvement in Striped Dolphins (Stenella coeruleoalba) with Morbilliviral Encephalitis","volume":"61","author":"Mazzariol","year":"2017","journal-title":"Acta Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.tim.2018.08.010","article-title":"New Insights into Measles Virus Brain Infections","volume":"27","author":"Watanabe","year":"2019","journal-title":"Trends Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/1348-0421.12949","article-title":"Molecular Signatures in Cetacean Morbillivirus and Host Species Proteomes: Unveiling the Evolutionary Dynamics of an Enigmatic Pathogen?","volume":"66","author":"Zinzula","year":"2022","journal-title":"Microbiol. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Pratakpiriya, W., Ping Teh, A.P., Radtanakatikanon, A., Pirarat, N., Thi Lan, N., Takeda, M., Techangamsuwan, S., and Yamaguchi, R. (2017). Expression of Canine Distemper Virus Receptor Nectin-4 in the Central Nervous System of Dogs. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-00375-6"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Busch, J., Chey, S., Sieg, M., Vahlenkamp, T.W., and Liebert, U.G. (2021). Mutated Measles Virus Matrix and Fusion Protein Influence Viral Titer in Vitro and Neuro-Invasion in Lewis Rat Brain Slice Cultures. Viruses, 13.","DOI":"10.3390\/v13040605"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e2026027118","DOI":"10.1073\/pnas.2026027118","article-title":"Fitness Selection of Hyperfusogenic Measles Virus F Proteins Associated with Neuropathogenic Phenotypes","volume":"118","author":"Ikegame","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e0052821","DOI":"10.1128\/JVI.00528-21","article-title":"CADM1 and CADM2 Trigger Neuropathogenic Measles Virus-Mediated Membrane Fusion by Acting in cis","volume":"95","author":"Shirogane","year":"2021","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e0194921","DOI":"10.1128\/jvi.01949-21","article-title":"Short-Stalk Isoforms of CADM1 and CADM2 Trigger Neuropathogenic Measles Virus-Mediated Membrane Fusion by Interacting with the Viral Hemagglutinin","volume":"96","author":"Takemoto","year":"2022","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5489","DOI":"10.1038\/s41467-023-41182-0","article-title":"Highly Pathogenic Avian Influenza A(H5N1) in Marine Mammals and Seabirds in Peru","volume":"14","author":"Leguia","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"852","DOI":"10.3201\/eid2904.221426","article-title":"Highly Pathogenic Avian Influenza A(H5N1) Virus in a Harbor Porpoise, Sweden","volume":"29","author":"Thorsson","year":"2023","journal-title":"Emerg. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Murawski, A., Fabrizio, T., Ossiboff, R., Kackos, C., Jeevan, T., Jones, J.C., Kandeil, A., Walker, D., Turner, J.C.M., and Patton, C. (2024). Highly Pathogenic Avian Influenza A(H5N1) Virus in a Common Bottlenose Dolphin (Tursiops truncatus) in Florida. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-06173-x"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102712","DOI":"10.1016\/j.tmaid.2024.102712","article-title":"Pacific and Atlantic Sea Lion Mortality Caused by Highly Pathogenic Avian Influenza A(H5N1) in South America","volume":"59","author":"Plaza","year":"2024","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.3201\/eid3008.240481","article-title":"Highly Pathogenic Avian Influenza Virus A(H5N1) Clade 2.3.4.4b Infection in Free-Ranging Polar Bear, Alaska, USA","volume":"30","author":"Stimmelmayr","year":"2024","journal-title":"Emerg. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sierra, E., Fern\u00e1ndez, A., Felipe-Jim\u00e9nez, I., Zucca, D., D\u00edaz-Delgado, J., Puig-Lozano, R., C\u00e2mara, N., Consoli, F., D\u00edaz-Santana, P., and Su\u00e1rez-Santana, C. (2020). Histopathological Differential Diagnosis of Meningoencephalitis in Cetaceans: Morbillivirus, Herpesvirus, Toxoplasma gondii, Brucella sp., and Nasitrema sp.. Front. Vet. Sci., 7.","DOI":"10.3389\/fvets.2020.00650"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1084\/jem.20021980","article-title":"Cellular Prion Protein Promotes Brucella Infection into Macrophages","volume":"198","author":"Watarai","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Angelucci, C.B., Giacominelli-Stuffler, R., Baffoni, M., Di Francesco, C.E., Di Francesco, G., Di Renzo, L., Tittarelli, M., Petrella, A., Grattarola, C., and Mazzariol, S. (2022). Cellular Prion Protein Expression in the Brain Tissue from Brucella ceti-Infected Striped Dolphins (Stenella coeruleoalba). Animals, 12.","DOI":"10.3390\/ani12101304"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rebollada-Merino, A., Giorda, F., Pumarola, M., Martino, L., Gomez-Buendia, A., Romani-Cremaschi, U., Casalone, C., Mattioda, V., Di Nocera, F., and Lucifora, G. (2024). Neurobrucellosis (Brucella ceti) in Striped Dolphins (Stenella coeruleoalba): Immunohistochemical Studies on Immune Response and Neuroinflammation. Vet. Pathol., epub ahead of print.","DOI":"10.1177\/03009858241250336"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/8\/684\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:36:18Z","timestamp":1760110578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/8\/684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,14]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["pathogens13080684"],"URL":"https:\/\/doi.org\/10.3390\/pathogens13080684","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,14]]}}}