Losartan Prevents Maladaptive Auditory-Somatosensory Plasticity After Hearing Loss via Transforming Growth Factor-β Signaling Suppression
| Autor: | Hyun Sang Cho, Mun Young Chang, Suk-Won Ahn, Jong Tae Baek, Seog Kyun Mun, Kyu-Hee Han |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Hearing loss Vesicular glutamate transporter 1 medicine.medical_treatment lcsh:Medicine Somatosensory system Cochlear nucleus Losartan 03 medical and health sciences Tinnitus 0302 clinical medicine Internal medicine medicine otorhinolaryngologic diseases Auditory-Somatosensory Plasticity 030223 otorhinolaryngology Hearing Loss Saline Cochlea biology business.industry lcsh:R lcsh:Otorhinolaryngology lcsh:RF1-547 Endocrinology Otorhinolaryngology 030220 oncology & carcinogenesis biology.protein Surgery Original Article medicine.symptom business medicine.drug |
| Zdroj: | Clinical and Experimental Otorhinolaryngology, Vol 12, Iss 1, Pp 33-39 (2019) Clinical and Experimental Otorhinolaryngology |
| ISSN: | 2005-0720 1976-8710 |
| Popis: | Objectives Hearing loss disrupts the balance of auditory-somatosensory inputs in the cochlear nucleus (CN) of the brainstem, which has been suggested to be a mechanism of tinnitus. This disruption results from maladaptive auditory-somatosensory plasticity, which is a form of axonal sprouting. Axonal sprouting is promoted by transforming growth factor (TGF)-β signaling, which can be inhibited by losartan. We investigated whether losartan prevents maladaptive auditory-somatosensory plasticity after hearing loss. Methods The study consisted of two stages: determining the time course of auditory-somatosensory plasticity following hearing loss and preventing auditory-somatosensory plasticity using losartan. In the first stage, rats were randomly divided into two groups: a control group that underwent a sham operation and a deaf group that underwent cochlea ablation on the left side. CNs were harvested 1 and 2 weeks after surgery. In the second stage, rats were randomly divided into either a saline group that underwent cochlear ablation on the left side and received normal saline or a losartan group that underwent cochlear ablation on the left side and received losartan. CNs were harvested 2 weeks after surgery. Hearing was estimated with auditory brainstem responses (ABRs). Western blotting was performed for vesicular glutamate transporter 1 (VGLUT1), reflecting auditory input; vesicular glutamate transporter 2 (VGLUT2), reflecting somatosensory input; growth-associated protein 43 (GAP-43), reflecting axonal sprouting; and p-Smad2/3. Results Baseline ABR thresholds before surgery ranged from 20 to 35 dB sound pressure level. After cochlear ablation, ABR thresholds were higher than 80 dB. In the first experiment, VGLUT2/VGLUT1 ratios did not differ significantly between the control and deaf groups 1 week after surgery. At 2 weeks after surgery, the deaf group had a significantly higher VGLUT2/VGLUT1 ratio compared to the control group. In the second experiment, the losartan group had a significantly lower VGLUT2/VGLUT1 ratio along with significantly lower p-Smad3 and GAP-43 levels compared to the saline group. Conclusion Losartan might prevent axonal sprouting after hearing loss by blocking TGF-β signaling thereby preventing maladaptive auditory-somatosensory plasticity. |
| Databáze: | OpenAIRE |
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