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The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
Published on: November 26, 2015
Long-lasting changes in the cochlear K+ recycling structures after acute energy failure
Yoichiro Takiguchi1, Guang-wei Sun, Kaoru Ogawa
1Department of Otolaryngology, Eiju General Hospital, 2-23-16 Higashi-ueno, Taito-ku, Tokyo 110-8645, Japan; The Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan; Department of Otolaryngology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Neuroscience Research
|July 6, 2013
Summary
Cochlear fibrocytes are crucial for hearing. Mitochondrial toxin 3-nitropropionic acid (3NP) causes hearing loss by damaging these cells, leading to long-lasting cochlear changes and potential compensation mechanisms.
Area of Science:
- Ototolaryngology
- Neuroscience
- Cell Biology
Background:
- Fibrocytes in the cochlear lateral wall and spiral limbus are vital for potassium transport and self-renewal.
- Acute energy failure in the cochlea can lead to hearing loss primarily due to cochlear fibrocyte degeneration.
Purpose of the Study:
- To investigate the long-term morphological and molecular consequences of induced cochlear energy failure.
- To understand the compensatory mechanisms in fibrocytes following severe cochlear damage.
Main Methods:
- Induction of long-lasting cochlear damage using a modified 3-nitropropionic acid (3NP) administration protocol in rats.
- Morphological and molecular analysis of cochlear tissues (spiral ligament, stria vascularis, spiral limbus) 16 weeks post-administration.
Main Results:
- Severe fibrocyte degeneration observed in the basal turn of the spiral ligament and middle/basal turns of the spiral limbus.
- Decreased Na,K-ATPase, NKCC1, Kir4.1, and L-PGDS levels, with increased connexin 26 (Cx26) in specific fibrocyte populations.
- Evidence of long-lasting molecular changes in the cochlear lateral wall and spiral limbus.
Conclusions:
- Induced cochlear energy failure leads to profound and persistent fibrocyte degeneration.
- Observed molecular changes suggest potential compensatory strategies for damaged potassium recycling and cellular protection against ATP depletion.
Keywords:
3-Nitropropionic acid3-nitropropionic acid3NPABRCochlear fibrocytesCx26Hearing lossKir4.1L-PGDSMitochondrial dysfunctionNKCC1Na-K-Cl cotransporter isoform 1PBSRecoverySSNHLStria vascularisan inwardly rectifying K(+) channelauditory brainstem responseconnexin 26lipocalin-type prostaglandin D synthasephosphate buffered salinesudden sensorineural hearing loss
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