title: Chronic hyperammonemia alters the circadian rhythms of corticosteroid hormone levels and of motor activity in rats.
abstract: Patients with liver cirrhosis may present hepatic encephalopathy with a wide range of neurological disturbances and alterations in sleep quality and in the sleep-wake circadian rhythm. Hyperammonemia is a main contributor to the neurological alterations in hepatic encephalopathy. We have assessed, in an animal model of chronic hyperammonemia without liver failure, the effects of hyperammonemia per se on the circadian rhythms of motor activity, temperature, and plasma levels of adrenal corticosteroid hormones. Chronic hyperammonemia alters the circadian rhythms of locomotor activity and of cortisol and corticosterone levels in blood. Different types of motor activity are affected differentially. Hyperammonemia significantly alters the rhythm of spontaneous ambulatory activity, reducing strongly ambulatory counts and slightly average velocity during the night (the active phase) but not during the day, resulting in altered circadian rhythms. In contrast, hyperammonemia did not affect wheel running at all, indicating that it affects spontaneous but not voluntary activity. Vertical activity was affected only very slightly, indicating that hyperammonemia does not induce anxiety. Hyperammonemia abolished completely the circadian rhythm of corticosteroid hormones in plasma, completely eliminating the peaks of cortisol and corticosterone present in control rats at the start of the dark period. The data reported show that chronic hyperammonemia, similar to that present in patients with liver cirrhosis, alters the circadian rhythms of corticosteroid hormones and of motor activity. This suggests that hyperammonemia would be a relevant contributor to the alterations in corticosteroid hormones and in circadian rhythms in patients with liver cirrhosis.
authors.affiliation: Departament de Biologie, Faculte des Sciences, Université Abdelmalek Essaadi, Tétouan, Maroc.
authors.forename: Hanan
authors.initials: H
authors.lastname: Ahabrach
authors.forename: Blanca
authors.initials: B
authors.lastname: Piedrafita
authors.forename: Abdelmalik
authors.initials: A
authors.lastname: Ayad
authors.forename: Nisrin
authors.initials: N
authors.lastname: El Mlili
authors.forename: Mohammed
authors.initials: M
authors.lastname: Errami
authors.forename: Vicente
authors.initials: V
authors.lastname: Felipo
authors.forename: Marta
authors.initials: M
authors.lastname: Llansola
mesh_terms: D000305:Adrenal Cortex Hormones / Q000032:analysis / Q000097:blood*; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000502:physiology; D002908:Chronic Disease; D002940:Circadian Rhythm / Q000502:physiology*; D003345:Corticosterone / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy / Q000097:blood* / Q000503:physiopathology; D006854:Hydrocortisone / Q000032:analysis / Q000097:blood; D022124:Hyperammonemia / Q000097:blood* / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009068:Movement / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000305:Adrenal Cortex Hormones; D003345:Corticosterone; D006854:Hydrocortisone