{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:52:11Z","timestamp":1791276731983,"version":"4.1.0"},"reference-count":161,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>The loss of a companion animal can provoke grief whose intensity rivals human bereavement, yet its biological basis remains largely uncharted. This structured narrative review synthesizes neurobiological, endocrinological, immunological, and psychosocial evidence into a mechanistic framework offered not as established fact but as a source of testable hypotheses. We trace the substrates of the human\u2013animal bond across six interacting systems and propose how disruption of each upon an animal\u2019s death may drive grief. Three carry comparatively robust analogical support (oxytocinergic signaling, hypothalamic\u2013pituitary\u2013adrenal [HPA] axis regulation, and neuroinflammatory activation) and three are more exploratory (dopaminergic, serotonergic, and endocannabinoid pathways). Integrating extracted study-level data into transparent prioritization heuristics, we identify the HPA axis, assessed with its coupled oxytocinergic partner, as the most defensible first target for a direct biomarker study, a conclusion robust across three methodologically independent analyses. No direct pet-loss evidence yet supports any proposal, and this gap is the review\u2019s central motivation. As applied context, we address euthanasia-related guilt, disenfranchised grief under East Asian norms (a tentative \u201cdouble disenfranchisement\u201d hypothesis that we put forward for testing), assessment instruments, evidence-graded therapies, priorities for developing Korean-language tools, and One Health research priorities.<\/jats:p>","DOI":"10.3390\/ani16193129","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:06:47Z","timestamp":1791274007000},"page":"3129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neurobiology of Pet Loss Grief: A Review from a One Health Perspective"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3256-4328","authenticated-orcid":false,"given":"Thanh Huu Phan","family":"Ngo","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9586-7337","authenticated-orcid":false,"given":"Jiwon","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1967-3603","authenticated-orcid":false,"given":"Hyeong Jun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5181-2135","authenticated-orcid":false,"given":"Wan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Republic of Korea"},{"name":"Section of Molecular and Cellular Medicine, Medical Institute of Dongguk University, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.2044-8295.1994.tb02522.x","article-title":"Bereavement following death of a pet","volume":"85","author":"Archer","year":"1994","journal-title":"Br. 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