Acute Hypoxia Induces Transient Olfactory Dysfunction through Olfactory Epithelial Degeneration and Bulbar Mitochondrial Stress in Zebrafish

Document Type

Article

Publication Date

7-1-2026

Publication Source

Eneuro

Volume Number

13

Issue Number

7

E-ISSN

23732822

Abstract

Hypoxic–ischemic injury is a major cause of olfactory dysfunction, yet the cellular and morphological mechanisms underlying this sensory loss remain poorly understood. Here, we investigated the structural, cellular, and functional effects of acute hypoxic exposure on the olfactory system of adult zebrafish (Danio rerio) of both sexes, a model organism with remarkable neuroregenerative capacity. Fish were subjected to 15 min of acute severe hypoxia (0.8 mg/L DO) and assessed at 1 and 5 d posthypoxia. We evaluated olfactory function by means of cadaverine-evoked aversive behavioral assays. Structural and morphological integrity and inflammation of the olfactory epithelium (OE) and olfactory bulb (OB) were characterized using immunohistochemistry, histological stainings, and a 2,3,5-triphenyltetrazolium chloride colorimetric assay. Acute hypoxic exposure impaired olfactory-mediated behaviors without affecting locomotion or exploratory behavior. In the peripheral OE, hypoxia caused neurodegeneration, disruption of the nasal mucus layer, and robust leukocytic infiltration. We observed reduced mitochondrial dehydrogenase activity in the OB along with reactive astrogliosis. Olfactory function recovered by 5 d, coinciding with full restoration of OE morphology, which was supported by a strong proliferative response. These findings reveal a coordinated degenerative and regenerative response to hypoxia across the olfactory axis, with implications for understanding hypoxia-induced sensory loss and neural repair.

Keywords

hypoxia, ischemia, neurodegeneration, neurogenesis, neuroinflammation, olfactory dysfunction, olfactory system, zebrafish

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