This mouse study delivered ferric ammonium citrate into the nose and followed iron along the olfactory route. Treated mice lost olfactory discrimination, accumulated iron in the olfactory mucosa and bulb, and showed immune-cell activation and selective loss of dopaminergic and glutamatergic neurons and oligodendrocytes, without signs of ferroptosis. Serum iron did not change and cerebrospinal fluid iron was undetectable, which the authors take as evidence of direct nerve transport.
Key numbers
- Dose: ferric ammonium citrate 200 mg/kg (250 mg/mL) intranasally, twice every other day; controls received saline (Methods).
- Olfactory bulb iron by ICP-MS: iron-56 up 59.66% and iron-57 up 56.52% versus controls, with a marginal rise in iron-54; n = 5 to 6 (Results; Fig. 2E).
- Iron-positive Perls staining in the olfactory bulb up 149.82% (Results; Fig. 2G).
- L-ferritin mRNA up 70.38% and protein up 54.52% in the olfactory bulb (Results; Fig. 2C, 2D).
- Serum iron unchanged; cerebrospinal fluid iron undetectable in all mice (Results; Fig. 2H).
Methods (brief)
Behavioral olfactory tests (n = 12), Perls-DAB and immunohistochemistry, ICP-MS of digested tissue, bulk RNA sequencing with immune-cell deconvolution, spatial transcriptomics of healthy bulbs, and western blots for ferroptosis and neuronal markers.
Evidence fitness
Supports animal evidence that iron reaching the nasal epithelium can accumulate in the olfactory bulb and damage specific neurons. It uses a high pharmacological dose of a soluble iron salt and does not represent measured environmental or occupational air exposure.
Limitations
Single dose regimen, male mice only, treatment duration shown only schematically, and percentage changes reported without absolute tissue concentrations in the text. The authors declared no competing interests.
Related evidence
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