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Downregulation of GJB2 and SLC26A4 genes induced by noise exposure is associated with cochlear damage

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Abstract

Background

Noise-induced hearing loss (NIHL) is one the major causes of acquired hearing loss in developed countries. Noise can change the pattern of gene expression, inducing sensorineural hearing impairment. There is no investigation on the effects of noise frequency on the expression of GJB2 and SLC26A4 genes involved in congenital hearing impairment in cochlear tissue. Here we investigated the impacts of white and purple noise on gene expression and pathologic changes of cochlear tissue.

Methods

In this study, 32 adult male Westar rats were randomly divided into experimental groups: WN, animals exposed to white noise with a frequency range of 100-20000 Hz; PN, animals exposed to purple noise with a frequency range of 4–20 kHz, and control group, without noise. The experimental groups were exposed to a 118–120 dB sound pressure level for 8 h per 3 days and 6 days. 1 h and 1 week after termination of noise exposure, cochlear tissue was prepared for pathology and gene expression analysis.

Results

Both white and purple noises caused permanent damage to the cortical, estrosilica systems of hair cells and ganglion of the hearing nerve. GJB2 and SLC26A4 were downregulated in both groups exposed with white and purple noise by increasing the time of noise exposure. However, differences are notably more significant in purple noise, which is more intensified. Also, 1 weak post noise exposure, the downregulation is remarkably higher than 1 h.

Conclusions

Our findings suggest that downregulation of GJB2 and SLC26A4 genes are associated with pathological injury in response to noise exposure in cochlear tissue. It would be suggested the demand for assessment of RNA and protein expression of genes involved in noise-induced hearing loss and subsequently the practice of hearing protection programs.

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Availability of data and materials

Data will be available on special request to corresponding author.

Abbreviations

GJB2:

Gap junction beta-2

SLC26A4:

Solute carrier family 26 member 4

NIHL:

Noise-induced hearing loss

PN:

Purple noise

WN:

White noise

dB:

Decibel

SIL:

Sound intensity level

SPL:

Sound pressure level

GADD45β:

Growth arrest and DNA damage inducible protein 45β

CDK:

Cyclin-dependent kinase

CIITA:

Class II transactivator

MHCII:

Major histocompatibility complex II

Cx26:

Connexin26

CRH:

Corticotropin-Releasing Hormone

Cfi:

Complement factor I

C1s:

Complement component 1, s subcomponent

IHC:

Inner hair cells

OHC:

Outer hair cells

PTS:

Permanent threshold shifts

PDS:

Pendred syndrome

PFA:

Paraformaldehyde

H&E:

Hematoxylin-Eosin

dNTP:

Deoxy Nucleoside Triphosphate

RT:

Reverse transcriptase

GAPDH:

Glyceraldehyde 3-Phosphate Dehydrogenase

ΔΔCt:

Delta-delta cycle threshold

HSP:

Heat shock proteins

MAPK:

Mitogen-activated protein kinase

CRH-R:

Corticotropin-releasing hormone receptor

SOD2:

Superoxide dismutase 2

CAT:

catalase

CX26:

Connexin 26

PTS:

Permanent hearing threshold

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Acknowledgements

The authors would like to express their gratitude to the Assistance of Research and Technology at Tehran University of Medical Sciences.

Funding

This research was supported by Tehran University of Medical Sciences & Health Services, Grant Numbers: 98-3-99-45886.

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Authors and Affiliations

  1. Department of Occupational Health and Safety Engineering, School of public health, Tehran University of Medical Sciences, Tehran, Iran

    Amir Abbasi Garmaroudi, Monireh Khadem, Maryam Mirzaei Hotkani, Sajjad Mozaffari & Mohammad Reza Monazzam Esmaeil poor

  2. Department of Medical Parasitology and Mycology, School of public health, Tehran University of Medical Sciences, Tehran, Iran

    Elham Kazemirad

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Contributions

AAG, MRME and EK collected and analyzed data. AAG and EK wrote the manuscript. MK, MMH and SM reviewed and revised the manuscript. EK and MRME supervised the entire processes. All authors read and approved the final manuscript.

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Correspondence to Mohammad Reza Monazzam Esmaeil poor or Elham Kazemirad.

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The authors declare that they have no competing of interest.

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The study was approved by the Ethics Research Committee of the School of Public Health, Tehran University of Medical Sciences (Code: IR.TUMS.SPH.REC.1398.220).

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Garmaroudi, A.A., Khadem, M., Hotkani, M.M. et al. Downregulation of GJB2 and SLC26A4 genes induced by noise exposure is associated with cochlear damage. Mol Biol Rep 49, 7219–7229 (2022). https://doi.org/10.1007/s11033-022-07291-7

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