ArticleClinical and experimental otorhinolaryngology2019
Losartan Prevents Maladaptive Auditory-Somatosensory Plasticity After Hearing Loss via Transforming Growth Factor-β Signaling Suppression.
Article in Clinical and experimental otorhinolaryngology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 12 citations in OpenAlex.
- Dual-Omics Mapping of Tinnitus Phenotype Transition in Noise-Exposed Auditory Cortex.Cellular and molecular neurobiology · 2025Article
- Role of microRNA‑375‑3p‑mediated regulation in tinnitus development.International journal of molecular medicine · 2021Article
- Changes in the Gene Expression Profiles of the Inferior Colliculus Following Unilateral Cochlear Ablation in Adult Rats.Biochemical genetics · 2021Article
- MicroRNAs Related to Cognitive Impairment After Hearing Loss.Clinical and experimental otorhinolaryngology · 2021Article
- Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus.PloS one · 2021Article
- Changes in microRNA Expression in the Cochlear Nucleus and Inferior Colliculus after Acute Noise-Induced Hearing Loss.International journal of molecular sciences · 2020Article
- Effect of myricetin on the gene expressions of NOX3, TGF-β1, prestin, and HSP-70 and anti-oxidant activity in the cochlea of noise-exposed rats.Iranian journal of basic medical sciences · 2020Article
- Noise exposure alters MMP9 and brevican expression in the rat primary auditory cortex.BMC neuroscience · 2020Article
- Axonal sprouting in the dorsal cochlear nucleus affects gap‑prepulse inhibition following noise exposure.International journal of molecular medicine · 2019Article
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6 authors at 4 institutions in 1 country.
Funding
Abstract
objectivesHearing 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.
methodsThe 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.
resultsBaseline 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.
conclusionLosartan might prevent axonal sprouting after hearing loss by blocking TGF-β signaling thereby preventing maladaptive auditory-somatosensory plasticity.
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