Abstract
Serotonin (5-HT) plays a crucial role in modulating the afferent fiber discharge rate in the inferior colliculus, auditory cortex, and other nuclei of the ascending auditory system. Resveratrol, a natural polyphenol phytoalexin, can inhibit serotonin transporters (SERT) to increase synaptic 5-HT levels. In this study, we investigated the effects of resveratrol on noise-induced damage in the serotonergic system. Male Sprague-Dawley rats were anaesthetized and exposed to an 8-kHz tone at 116 dB for 3.5 h. Resveratrol (30 mg/kg, intraperitoneal injection [IP]) and citalopram (20 mg/kg, IP), a specific SERT inhibitor used as a positive control, were administered once a day for four consecutive days, with the first treatment occurring 2 days before noise exposure. Auditory brainstem response testing and positron emission tomography (PET) with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM, a specific radioligand for SERT) were used to evaluate functionality of the auditory system and integrity of the serotonergic system, respectively, before and after noise exposure. Finally, immunohistochemistry was performed 1 day after the last PET scan. Our results indicate that noise-induced serotonergic fiber loss occurred in multiple brain regions including the midbrain, thalamus, hypothalamus, striatum, auditory cortex, and frontal cortex. This noise-induced damage to the serotonergic system was ameliorated in response to treatment with resveratrol and citalopram. However, noise exposure increased the hearing threshold in the rats regardless of drug treatment status. We conclude that resveratrol has protective effects against noise-induced loss of SERT.
Highlights
Noise-induced hearing loss is one of the most prevalent occupational health hazards worldwide [1]
After exposure to narrowband noise (8 kHz, 116 dB) for 3.5 h, the hearing thresholds of rats in all noise exposure (NE) groups with or without drug treatment were elevated to 70.6 ± 15.8 dB on day 2 and recovered to approximately 51.3 ± 7.9 dB on day 8 until day 29, when the last auditory brainstem response (ABR) test was performed (Figure 1)
5-HT levels would reduce the noise-induced excitotoxicity of afferent auditory nerves by modulating glutamate neurotransmission through the 5-HT receptors in the brain regions of the auditory pathway
Summary
Noise-induced hearing loss is one of the most prevalent occupational health hazards worldwide [1]. Loud noise contributes to afferent dendrite swelling underneath. Molecules 2019, 24, 1344 the inner hair cells and mechanical damage to the outer hair cells [2]. The major excitatory neurotransmitter for inner hair cell–auditory nerve synapses, has been reported to cause noise-induced dendrite damage [3]. Glutamate excitotoxicity has been suggested as being attributed to noise-induced hearing loss. Various mechanisms underlying noise-induced adjacent neuronal death caused by glutamate excitotoxicity have been proposed, including elevation of intracellular calcium, accumulation of oxidizing free radicals, impairment of mitochondrial function, and activation of apoptotic and autophagic programs [4]. We found that serotonergic fibers were markedly reduced by 30–52% in various rat brain regions 4 weeks after noise exposure
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
