Single or Repeated Ablation of Mouse Olfactory Epithelium by Methimazole

Abstract

Odor-detecting olfactory sensory neurons residing in the nasal olfactory epithelium (OE) are the only neurons in direct contact with the external environment. As a result, these neurons are subjected to chemical, physical, and infectious insults, which may be the underlying reason why neurogenesis occurs in the OE of adult mammals. This feature makes the OE a useful model for studying neurogenesis and neuronal differentiation, with the possibility for systemic as well as local administration of various compounds and infectious agents that may interfere with these cellular processes. Several different chemical compounds have been shown to cause toxic injury to the OE, which can be used for OE ablation. We, and others, have found that the systemic administration of the hyperthyroid drug, methimazole, reliably causes olfactotoxicity as a side effect. Here, we outline an OE lesioning protocol for single or repeated ablation by methimazole. A single methimazole administration can be used to study neuroepithelial regeneration and stem cell activation, while repeated ablation and regeneration of OE enable the study of tissue stem cell exhaustion and generation of tissue metaplasia.

Pcdh19 mediates olfactory sensory neuron coalescence during postnatal stages and regeneration

“…Two to three month-old littermates were weighed and injected intraperitoneally with methimazole (100 mg/kg). We found, as previously described in other studies, 30 more consistent ablation of more ventral OSNs with a higher dose of methimazole. Mice were allowed to recover for four or seven weeks prior to sacrifice.…”

“…We treated two to three-month-old mutant and control littermates with methimazole, a drug that induces widespread ablation of OSNs and subsequent regeneration. 30 We optimized the amount of methimazole to ensure consistent ablation of the epithelium in our mice ( Figure S3 ). Although we cannot guarantee complete ablation, this treatment severely disrupted epithelial structure and coalescence.…”

The Nasal Solitary Chemosensory Cell Signaling Pathway Triggers Mouse Avoidance Behavior to Inhaled Nebulized Irritants

“…After methimazole injury, the MOE completely regenerates in approximately one month, while OSNs make synaptic contacts with mitral cells in the olfactory bulb at approximately one to two weeks ( Suzukawa et al, 2011 ). We performed ablation of the OE as previously described by intraperitoneal injection of methimazole (75 mg/kg) in 0.9% saline ( Håglin et al, 2021 ). In brief, 75 mg/kg methimazole was prepared under aseptic conditions in sterile physiological saline on the same day as the injections.…”

Zika virus leads to olfactory disorders in mice by targeting olfactory ensheathing cells

“…For viral RNA detection, serum samples and various tissues were collected at the indicated time points. RE, lung, OE, OB and brain tissues were isolated and weighted as previous described, 63 , 64 and stored at −80 °C until RNA extraction and quantitative real-time PCR (qRT–PCR) analyses (n = 3 per group). In addition, the brains of the mice were dissected and fixed in 4% paraformaldehyde (PFA) fixative solution for paraffin embedding and further detection.…”