Biology subjects

Calvo-Ochoa, E.

Publications and source records attributed to Calvo-Ochoa, E..

3 recordsLinked to original sources

bioRxiv2026

Acute hypoxia induces transient olfactory dysfunction through olfactory epithelial degeneration and bulbar mitochondrial stress in zebrafish

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 minutes of acute severe hypoxia (0.8 mg/L dissolved oxygen) and assessed at 1 and 5 days post-hypoxia (dph). 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 (TTC) 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 olfactory bulb (OB) along with reactive astrogliosis. Olfactory function recovered by 5 days, coinciding with full restoration of OE morphology, and 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. SIGNIFICANCEThis work addresses an important gap in knowledge regarding the mechanisms linking hypoxic insult and olfactory dysfunction. By using adult zebrafish, an extraordinarily regenerative vertebrate, it also provides insight into neuronal repair and regenerative processes supporting olfactory recovery. The novelty of our study resides in that, to our knowledge, there are no studies that provide a comprehensive characterization of the effects of hypoxia in the olfactory system across molecular, histological, and functional levels. These findings advance our understanding of hypoxia-induced sensory neurodegeneration and regeneration, and highlight the zebrafish olfactory system as a powerful model for investigating neural repair mechanisms relevant to hypoxic-ischemic brain injury.

neuroscience↗

bioRxiv2025

Olfactory dysfunction in a novel model of prodromal Parkinson's disease in adult zebrafish

Olfactory dysfunction is an early clinical marker of prodromal Parkinsons disease (PD), yet the underlying mechanisms remain unclear. To explore this relationship, we developed a zebrafish model that recapitulates prodromal PD-associated olfactory impairment without affecting motor function. We used zebrafish, due to their olfactory systems similarity to mammals and their unique nervous system regenerative capacity. By injecting 6-hydroxydopamine (6-OHDA) into the dorsal telencephalic ventricle, we observed a significant loss of dopaminergic (DA) periglomerular neurons in the olfactory bulb (OB) and retrograde degeneration of olfactory sensory neurons (OSNs) in the olfactory epithelium (OE). These alterations led to impaired responses to cadaverine, an aversive odorant, while responses to alanine, an attractive odorant, remained intact. 6-OHDA triggered robust neuroinflammatory responses that was attenuated by pranlukast, an anti-inflammatory drug. By 7 days post-injection, dopaminergic synapses in the OB were remodeled, OSNs in the OE appeared recovered, and neuroinflammation subsided, leading to full recovery of olfactory responses to cadaverine. These findings highlight zebrafish remarkable neuroplasticity and suggest this novel model of prodromal PD could provide valuable insights into early PD pathology. Understanding the interplay between dopaminergic loss, neuroinflammation, and olfactory dysfunction may inform therapeutic strategies for PD patients suffering from olfactory dysfunction.

neuroscience↗

bioRxiv2024

Structural regeneration and functional recovery of the olfactory system of zebrafish following brain injury

Olfactory dysfunction is a common outcome of brain injuries, negatively affecting quality of life. The mammalian nervous system has limited capacity for spontaneous olfactory recovery, making it challenging to study olfactory regeneration and recovery in adults. In contrast, zebrafish are an ideal model for such studies due to its extensive and lifelong regenerative abilities. In this work, we describe a model of excitotoxic injury in the olfactory bulb using quinolinic acid (QA) lesions in adult zebrafish. We observed extensive neurodegeneration in both the olfactory bulb and olfactory epithelium, including a reduction of bulbar volume, neuronal death, and impaired olfactory function. Recovery mechanisms involved tissue remodeling, cell proliferation, neurogenesis, leading to full restoration of olfactory function by 21 days. This study provides a model to further investigate the effects of excitotoxicity on olfactory dysfunction, and highlights zebrafishs remarkable regenerative abilities, providing insights into potential therapeutic strategies for restoring olfactory function following brain injuries.

neuroscience↗