Change in gene expression levels of GABA, glutamate and neurosteroid pathways due to acoustic trauma in the cochlea

Abstract

The characteristic feature of noise-induced hearing loss (NIHL) is the loss or malfunction of the outer hair cells (OHC) and the inner hair cells (IHC) of the cochlea. 90–95% of the spiral ganglion neurons, forming the cell bodies of cochlear nerve, synapse with the IHCs. Glutamate is the most potent excitatory neurotransmitter for IHC-auditory nerve synapses. Excessive release of glutamate in response to acoustic trauma (AT), may cause excitotoxicity by causing damage to the spiral ganglion neurons (SGN) or loss of the spiral ganglion dendrites, post-synaptic to the IHCs. Another neurotransmitter, GABA, plays an important role in the processing of acoustic stimuli and central regulation after peripheral injury, so it is potentially related to the regulation of hearing function and sensitivity after noise. The aim of this study is to evaluate the effect of AT on the expressions of glutamate excitotoxicity, GABA inhibition and neurosteroid synthesis genes.

We exposed 24 BALB/c mice to AT. Controls were sacrificed without exposure to noise, Post-AT(1) and Post-AT(15) were sacrificed on the 1st and 15th day, respectively, after noise exposure. The expressions of various genes playing roles in glutamate, GABA and neurosteroid pathways were compared between groups by real-time PCR.

Expressions of Cyp11a1, Gls, Gabra1, Grin2b, Sult1a1, Gad1, and Slc1a2 genes in Post-AT(15) mice were significantly decreased in comparison to control and Post-AT(1) mice. No significant differences in the expression of Slc6a1 and Slc17a8 genes was detected.

These findings support the possible role of balance between glutamate excitotoxicity and GABA inhibition is disturbed during the post AT days and also the synthesis of some neurosteroids such as pregnenolone sulfate may be important in this balance.

Keywords:

• Acoustic trauma
• GABA
• glutamate
• neurosteroid
• gene expression

Acknowledgements

We thank the Scientific Research Projects Unit of Erciyes University, Genome and Stem Cell Center and Erciyes University Experimental Application and Research Center in Kayseri.

Ethical approval

All experimental protocols used in this study were examined and approved by Erciyes University Animal Experiments Local Ethics Committee and performed in accordance with Guiding Principles for Research Involving Animals and Human Beings, Recommendations from the Declaration of Helsinki.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research which numbered TTU- 2017–7314 was supported by the Scientific Research Projects Unit of Erciyes University.