Differential Activating Effects of Thyrotropin-Releasing Hormone and its Analog Taltirelin on Motor Output to the Tongue Musculature In-Vivo.

Differential Activating Effects of Thyrotropin-Releasing Hormone and its Analog Taltirelin on Motor Output to the Tongue Musculature In-Vivo.:

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Differential Activating Effects of Thyrotropin-Releasing Hormone and its Analog Taltirelin on Motor Output to the Tongue Musculature In-Vivo.

Sleep. 2020 Mar 28;:

Authors: Liu WY, Liu H, Aggarwal J, Huang ZL, Horner RL

Abstract

Thyrotropin-releasing hormone (TRH) is produced by the hypothalamus but most brain TRH is located elsewhere where it acts as a neuromodulator. TRH-positive neurons project to the hypoglossal motoneuron pool where TRH receptor RNA shows a high degree of differential expression compared to the rest of the brain. Strategies to modulate hypoglossal motor activity are of physiological and clinical interest given the potential for pharmacotherapy for obstructive sleep apnea, a common and serious respiratory disorder. Here we identified the effects on tongue motor activity of TRH and a specific analog (taltirelin) applied locally to the hypoglossal motoneuron pool and systemically in-vivo. Studies were performed under isoflurane anesthesia and across sleep-wake states in rats. In anesthetized rats, microperfusion of TRH (n=8) or taltirelin (n=9) into the hypoglossal motoneuron pool caused dose dependent increases in tonic and phasic tongue motor activity (both P<0.001). However, the motor responses to TRH were biphasic, being significantly larger 'early' in the response vs. at the end of the intervention (P≤0.022). In contrast, responses to taltirelin were similar 'early' vs. 'late' (P≥0.107); i.e., once elicited the motor responses to taltirelin were sustained and maintained. In freely-behaving conscious rats (n=10), microperfusion of 10μM taltirelin into the hypoglossal motoneuron pool increased tonic and phasic tongue motor activity in non-REM sleep (P≤0.038). Intraperitoneal injection of taltirelin (1mg/kg, n=16 rats) also increased tonic tongue motor activity across sleep-wake states (P=0.010). These findings inform studies in humans to identify the potential beneficial effects of taltirelin for breathing during sleep and obstructive sleep apnea.

PMID: 32227104 [PubMed - as supplied by publisher]