Effects of fluoxetine on the gene expression of hippocampus and gap inhibition in noise-induced hearing loss rats

Objective

Fluoxetine was reported to restore critical period-like neural plasticity via alleviating perineuronal nets (PNNs). This study aimed to investigate the effect of fluoxetine on auditory processing and PNNs in auditory cortex and hippocampus.

Methods

Sprague-Dawley rats were exposed 2–20 kHz, 115 dB sound pressure level noise for 3 h per day from postnatal day 1–3 to postnatal day 21. After completion of noise exposure, 10 mg/kg/day of fluoxetine was administered for 19 days. There were four groups of rats according to the presence of noise exposure and fluoxetine treatment, vehicle, noise + vehicle, fluoxetine, and noise + fluoxetine rats. The gene expression changes of hippocampus were analyzed using RNA sequencing.

Results

In the auditory cortex, the expression of aggrecan (ACAN) was lower in noise-exposed rats than vehicle rats, while the noise + fluoxetine rats presented higher expression levels of ACAN which was comparable with that of the vehicle rats (p = 0.01 in Mann-Whitney U test; 146 ± 15 vs. 100 ± 11). In the hippocampus, the expression of brain-derived neurotrophic factor (BDNF) was lower in noise + vehicle rats while noise + fluoxetine rats presented higher expression of BDNF than noise + vehicle rats (p < 0.001 in Mann-Whitney U test; 389 ± 21 vs. 249 ± 16). The RNA sequencing of the hippocampus predicted the down regulation of genes involving extracellular matrix organization when compared noise + vehicle vs. noise + fluoxetine rats.

Conclusion

The fluoxetine administration in noise exposed rats improved the gap inhibition ability. The noise exposure decreased expression of BDNF and modulated the expression of genes related with extracellular matrix organization which was partially reversed after fluoxetine treatment.