Ultrasound modulation of melatonin release from pineal glands in vitro

Ultrasonics. 2025 Jan 5:148:107565. doi: 10.1016/j.ultras.2025.107565. Online ahead of print.

Abstract

Objectives: In this study, we aim to investigate whether therapeutic ultrasound can modulate the release of melatonin from the pineal gland-either increasing or decreasing its levels-and to assess the safety of this technique. This research could address a significant clinical need by providing a noninvasive method to potentially regulate sleep and circadian rhythms through the targeted modulation of melatonin.

Methods: Rat pineal glands were placed in a well with a Krebs Ringer Buffer solution. Ultrasound was applied to the glands using unfocused transducers set at an average intensity of 1 W/cm2 and three different frequencies (400, 600, and 800 kHz) with continuous exposure for 5 min. Fluid samples were collected from the well before (t = 0 min), immediately after (t = 5 min), and 30 min post-ultrasound treatment (t = 30 min). Melatonin release was subsequently measured using an ELISA kit and analyzed statistically. In addition, histological analysis was completed to determine any structural abnormalities due to ultrasound application.

Results: In the 600 kHz group there was a statistically significant decrease from t = 0 min to t = 5 min. No other statistically significant differences were observed. In addition, no histological changes were observed in the pineal glands due to ultrasound application.

Conclusions: This study indicated that ultrasound may be able to modulate melatonin release, however follow-up studies are necessary to determine optimal ultrasound parameters for this application.

Keywords: Melatonin; Pineal gland; Therapeutic ultrasound.