Intranasal administration of rotenone in mice attenuated olfactory functions through the lesion of dopaminergic neurons in the olfactory bulb.
Many environmental chemicals are thought to affect brain function. It was reported that chemicals in the nasal cavity directly reach the brain through the connection between olfactory neurons and the olfactory bulb (OB). In this 'olfactory transport,' xenobiotics absorbed at the nasal mucosa reach the brain by bypassing some physical barriers and defenses, and thus olfactory transport is suspected to be a vulnerable mechanism of the brain against invasion threats of environmental chemicals. In this study, we focused on the neuronal toxicity of rotenone administered intranasally to mice. The results showed that the mice that were administered rotenone had attenuated olfactory functions. We also found that intranasally administered rotenone induced acute mitochondrial stress at the OB. The repeated administration of rotenone resulted in a decrease in the number of dopaminergic neurons, which are inhibitory interneurons in the OB. Taken together, our findings suggest that the inhalation of environmental toxins induces the neurodegeneration of cranial neurons through olfactory transport, and that olfactory dysfunction may be induced as an earliest symptom of neurodegeneration caused by inhaled neurotoxins.
Department of Physiology, Division of Sensory Physiology, Asahikawa Medical University, Asahikawa, Japan.
Hitoshi
H
Sasajima
Department of Physiology, Division of Sensory Physiology, Asahikawa Medical University, Asahikawa, Japan.
Sadaharu
S
Miyazono
Department of Physiology, Division of Sensory Physiology, Asahikawa Medical University, Asahikawa, Japan.
Tomohiro
T
Noguchi
Department of Physiology, Division of Sensory Physiology, Asahikawa Medical University, Asahikawa, Japan. Electronic address: yanagi@asahikawa-med.ac.jp.
Makoto
M
Kashiwayanagi
D000281:Administration, Intranasal; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D020148:Butyric Acid / Q000008:administration & dosage; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism; D009830:Olfactory Bulb / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism; D012402:Rotenone / Q000008:administration & dosage / Q000633:toxicity*; D012903:Smell / Q000187:drug effects* / Q000502:physiology; D013312:Stress, Physiological / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
D020148:Butyric Acid; D011494:Protein Kinases; D012402:Rotenone; D014446:Tyrosine 3-Monooxygenase; D044767:Ubiquitin-Protein Ligases; D051028:bcl-2-Associated X Protein; D000099202:PTEN-Induced Putative Kinase; C494827:Bax protein, mouse; C111567:parkin protein
Dopaminergic neurons; Intranasal administration; Mitochondrial stress; Olfactory bulb; Olfactory transport; Rotenone