Age-Related Cochlear Synaptopathy in Rats: The Use of Short-Latency Auditory Evoked Potentials
Aging; Cochlear Synaptopathy; Rats.
Introduction: In the natural aging process, a decrease in synapses occurs between inner hair cells and spiral ganglion neurons of the auditory nerve, a phenomenon known as cochlear synaptopathy (CS). Studies suggest that short-latency auditory evoked potentials (AEP) can identify CS, but there are still gaps in the protocols and parameters used for this identification in clinical practice.Objective: To evaluate the applicability of short-latency AEPs in identifying aging-related CS in rodents. Method: Two studies were conducted. The first was a systematic literature review, registered in PROSPERO (CRD42025615318), aiming to synthesize data on the sensitivity of short-latency AEPs in identifying CS in aging rodents. The review followed the recommendations of the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA), with searches conducted in the PUBMED/MEDLINE, Cochrane Library, Scopus, Embase, Web of Science, Scielo, and LILACS databases, as well as gray literature. Article selection was performed independently and blindly by two reviewers, with the assistance of Rayyan and EndNote tools. The second study was a cross-sectional observational study, approved by the Animal Use Ethics Committee (protocol No. 2024-02-ISD). Ten healthy Wistar rats of both sexes, with no prior noise exposure, were used and divided into age groups: G1 (3–4 months), G2 (10 months), G3 (14–15 months), and G4 (24 months). The animals underwent auditory brainstem response (ABR) recording using the Eclipse equipment (EP25 model) under sedation. Electrodes were positioned at Fz (active), M1 and M2 (references), and the right paw (ground), with impedance below 5 kΩ. Click stimuli with alternating polarity at 90, 85, and 80 dBnHL were presented to each ear through 3A insert earphones at stimulation rates of 33.1, 15.1, and 7.1 clicks/s. The amplitudes of waves I and IV were analyzed blindly by two specialists. Data underwent descriptive and inferential statistical analysis in SPSS, adopting p<0.05. Results: In Study 1, 2,684 articles were identified, of which 15 were included. The most used model was the mouse (n=13), followed by Fisher 344 rats (n=1) and Wistar rats (n=1), with ages ranging from 3 to 33 months. All studies used ABR to identify CS, with wave I amplitude being the most frequent biomarker, and all confirmed CS through neurobiological analysis. In Study 2, examiner agreement was excellent (>90%). The mean amplitude was 1.33±0.69 μV for wave I and 0.75±0.62 μV for wave IV. Age did not influence the results, but a sex effect was observed. Wave I showed greater amplitude at 7.1 clicks/s compared to 33.1 clicks/s. Conclusion: Short-latency AEP demonstrated applicability in identifying CS in rodents, with wave I amplitude as a relevant biomarker and a significant effect of stimulation rate. The findings reinforce the use of ABR in CS investigation and provide insights for future studies.