Hyperammonaemia disrupts daily rhythms reversibly by elevating glutamate in the central circadian pacemaker.

ABSTRACT: Patients with cirrhosis exhibit features of circadian disruption. Hyperammonaemia has been suggested to impair both homeostatic and circadian sleep regulation. Here, we tested if hyperammonaemia directly disrupts circadian rhythm generation in the central pacemaker, the suprachiasmatic nuclei (SCN) of the hypothalamus. Wheel-running activity was recorded from mice fed with a hyperammonaemic or normal diet for ~35 days in a 12:12 light-dark (LD) cycle followed by ~15 days in constant darkness (DD). The expression of the clock protein PERIOD2 (PER2) was recorded from SCN explants before, during and after ammonia exposure, ±glutamate receptor antagonists. In LD, hyperammonaemic mice advanced their daily activity onset time by ~1 h (16.8 ± 0.3 vs. 18.1 ± 0.04 h, p = .009) and decreased their t

SUBMITTER: Granados-Fuentes D 

PROVIDER: S-EPMC9974605 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature