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.

Differential role of interleukin‐1β in neuroinflammation‐induced impairment of spatial and nonspatial memory in hyperammonemic rats

“…No difference in object preference was observed between control and hyperammonemic rats. There were also no differences during the day, when behavioral tasks were performed, between control and hyperammonemic rats on locomotoive activity as reported for ambulatory counts, ambulatory distance, and velocity in the same rat model by Ahabrach et al (42).…”

GR3027 antagonizes GABAAreceptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy

“…Motor activity was recorded continuously at intervals of 5 min for 14 days in a 12:12-h light-dark cycle with an actimeter of infrared motion detection as in Ahabrach et al ( 1 ). Ambulatory counts and vertical counts were recorded ( 1 ). Activity was detected by arrays of infrared motion detection, with two arrays 1 cm above the floor of the chamber and another array 6 cm above the floor.…”

An Inhibitor of Neuronal Exocytosis (DD04107) Displays Long-Lasting In Vivo Activity against Chronic Inflammatory and Neuropathic Pain

“…One ambulatory count was recorded when the rats interrupted three consecutive infrared beams. One vertical count was recorded when the rats activated the above detectors (Ahabrach et al, 2010). For all of these locomotor tests, DD04107 was administered at 10 mg/kg s.c.…”