Acute N-Acetylcysteine Administration Ameliorates Loss of Olfactory Neurons Following Experimental Injury In Vivo

Stefania Goncalves, Bradley J. Goldstein

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The olfactory epithelium (OE) is the peripheral organ for the sense of smell, housing primary sensory neurons that project axons from the nose to the brain. Due to the presence of a basal stem cell niche, the adult mammalian OE is a dynamic tissue capable of replacing neurons following their loss. Nonetheless, certain conditions, such as blunt head trauma, can result in persistent olfactory loss, thought to be due to shearing of olfactory nerve filaments at the skull base, degeneration, and failures in proper regeneration/reinnervation. The identification of new treatment strategies aimed at preventing degeneration of olfactory neurons is, therefore, needed. In considering potential therapies, we have focused on N-acetylcysteine (NAC), a glutathione substrate shown to be neuroprotective, with a record of safe clinical use. Here, we have tested the use of NAC in an animal model of olfactory degeneration. Administered acutely, we found that NAC (100 mg/kg, twice daily) resulted in a reduction of olfactory neuronal loss from the OE of the nose following surgical ablation of the olfactory bulb. At 1 week postlesion, we identified 54 ± 8.1 mature neurons per 0.5 mm epithelium in NAC-treated animals vs. 28 ± 4.2 in vehicle-treated controls (P = 0.02). Furthermore, in an olfactory cell culture model, we have identified significant alterations in the expression of several genes involved in oxidative stress pathways following NAC exposure. Our results provide evidence supporting the potential therapeutic utility for NAC acutely following head trauma-induced olfactory loss. Anat Rec, 303:626–633, 2020.

Original languageEnglish (US)
Pages (from-to)626-633
Number of pages8
JournalAnatomical Record
Volume303
Issue number3
DOIs
StatePublished - Mar 1 2020

Keywords

  • n-acetylcysteine
  • neurons
  • olfaction
  • oxidative stress
  • regeneration

ASJC Scopus subject areas

  • Anatomy
  • Biotechnology
  • Histology
  • Ecology, Evolution, Behavior and Systematics

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