title: Sensory deprivation disrupts homeostatic regeneration of newly generated olfactory sensory neurons after injury in adult mice.
abstract: Although it is well known that injury induces the generation of a substantial number of new olfactory sensory neurons (OSNs) in the adult olfactory epithelium (OE), it is not well understood whether olfactory sensory input influences the survival and maturation of these injury-induced OSNs in adults. Here, we investigated whether olfactory sensory deprivation affected the dynamic incorporation of newly generated OSNs 3, 7, 14, and 28 d after injury in adult mice. Mice were unilaterally deprived of olfactory sensory input by inserting a silicone tube into their nostrils. Methimazole, an olfactotoxic drug, was also injected intraperitoneally to bilaterally ablate OSNs. The OE was restored to its preinjury condition with new OSNs by day 28. No significant differences in the numbers of olfactory marker protein-positive mature OSNs or apoptotic OSNs were observed between the deprived and nondeprived sides 0-7 d after injury. However, between days 7 and 28, the sensory-deprived side showed markedly fewer OSNs and mature OSNs, but more apoptotic OSNs, than the nondeprived side. Intrinsic functional imaging of the dorsal surface of the olfactory bulb at day 28 revealed that responses to odor stimulation were weaker in the deprived side compared with those in the nondeprived side. Furthermore, prevention of cell death in new neurons 7-14 d after injury promoted the recovery of the OE. These results indicate that, in the adult OE, sensory deprivation disrupts compensatory OSN regeneration after injury and that newly generated OSNs have a critical time window for sensory-input-dependent survival 7-14 d after injury.
authors: Department of Otolaryngology and Department of Physiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, sh-kiku@m.u-tokyo.ac.jp.
authors: Shu
authors: S
authors: Kikuta
authors: Department of Otolaryngology and.
authors: Takashi
authors: T
authors: Sakamoto
authors: Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, Houston, Texas 77030, and.
authors: Shin
authors: S
authors: Nagayama
authors: Department of Otolaryngology and.
authors: Kaori
authors: K
authors: Kanaya
authors: Department of Otolaryngology and.
authors: Makoto
authors: http://orcid.org/0000-0001-5447-7232
authors: M
authors: Kinoshita
authors: Department of Otolaryngology and.
authors: Kenji
authors: K
authors: Kondo
authors: Department of Artificial Organs and Medical Device Creation, National Institute of Sensory Organs, Tokyo Medical Center, National Hospital Organization, Meguro-ku, Tokyo 152-8902, Japan.
authors: Koichi
authors: K
authors: Tsunoda
authors: Department of Physiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Kensaku
authors: K
authors: Mori
authors: Department of Otolaryngology and.
authors: Tatsuya
authors: T
authors: Yamasoba
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000633:toxicity; D017209:Apoptosis / Q000502:physiology; D061945:Caspase Inhibitors / Q000494:pharmacology; D049109:Cell Proliferation; D002470:Cell Survival; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D008713:Methimazole / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000502:physiology*; D009831:Olfactory Mucosa / Q000187:drug effects; D018034:Olfactory Receptor Neurons / Q000293:injuries* / Q000502:physiology*; D012683:Sensory Deprivation / Q000502:physiology*
chemical_list: D013956:Antithyroid Agents; D061945:Caspase Inhibitors; D008713:Methimazole
keywords: apoptosis; homeostatic regeneration; olfactory epithelium; olfactory sensory neuron; sensory deprivation