RT Journal Article
SR Electronic
T1 Differential Effects of Nasal Inflammation and Odor Deprivation on Layer-Specific Degeneration of the Mouse Olfactory Bulb
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0403-19.2020
DO 10.1523/ENEURO.0403-19.2020
VO 7
IS 2
A1 Sanae Hasegawa-Ishii
A1 Fumiaki Imamura
A1 Shin Nagayama
A1 Makiko Murata
A1 Atsuyoshi Shimada
YR 2020
UL http://www.eneuro.org/content/7/2/ENEURO.0403-19.2020.abstract
AB Harmful environmental agents cause nasal inflammation, and chronic nasal inflammation induces a loss of olfactory sensory neurons (OSNs) and reversible atrophy of the olfactory bulb (OB). Here, we investigated the mechanisms underlying this inflammation-induced OB atrophy by histologically and biochemically comparing the OB changes in mouse models of nasal inflammation and odor deprivation. In addition, we examined whether odor stimulation is necessary for OB recovery from atrophy. One group of adult male C57BL/6 mice was administered lipopolysaccharide (LPS) unilaterally for 10 weeks to induce nasal inflammation (control animals received saline), and a second group received unilateral naris closures (NCs) for 10 weeks of odor deprivation. The OBs atrophied in both models, but odor deprivation shrank the glomerular, external plexiform, mitral, and granule cell layers (GCLs), whereas the olfactory nerve, glomerular, and external plexiform layers (EPLs) atrophied as a result of nasal inflammation. Additionally, nasal inflammation, but not odor deprivation, caused neuroinflammation in the OB, inducing glial activation and elevated expression of interleukin-1β (IL-1β) and TNFα. After 10 weeks of nasal inflammation, mice were housed for another 10 weeks with no additional treatment or with unilateral NC. Nasal inflammation and glial activation subsided in both groups, but glomerular and EPLs recovered only in those with no additional treatment. Our findings demonstrate that nasal inflammation and odor deprivation differentially induce layer-specific degeneration in the OB, that loss of OSN activity rather than neuroinflammation is a major cause of inflammation-induced OB atrophy, and that odor stimulation is required for OB recovery from atrophy.